Publications by authors named "Neil Binkley"

204 Publications

A pilot study comparing daily teriparatide with monthly cycles of teriparatide and raloxifene.

Arch Osteoporos 2021 Apr 15;16(1):70. Epub 2021 Apr 15.

Osteoporosis Clinical Research Program, University of Wisconsin-Madison, 2870 University Ave, Suite 100, Madison, WI, 53705, USA.

This 6-month pilot study in osteoporotic postmenopausal women evaluated cyclic TPD/RLX compared to daily subcutaneous TPD with the concept of optimizing bone formation. Compared to daily subcutaneous TPD, cyclic therapy showed comparable increase in spine BMD and favorable effects on total proximal femur BMD and cortical thickness.

Purpose: There is no cure for osteoporosis; better medications or different approaches with current agents are needed. We hypothesized that monthly cycles of teriparatide (TPD) followed by raloxifene (RLX) might promote ongoing bone formation. Additionally, as TPD might initially adversely affect hip BMD, such effects may be mitigated by a cyclic approach. Therefore, this 6-month pilot study evaluated the effect of cyclic TPD/RLX compared to daily subcutaneous TPD on bone markers, BMD, trabecular bone score (TBS), and hip parameters assessed by 3D modeling.

Methods: Postmenopausal osteoporotic women (n=26) were randomized to open-label TPD 20 daily or alternating monthly cycles of TPD followed by monthly RLX 60 mg daily. BMD was measured at the lumbar spine (LS), femur, and radius by DXA. To further assess LS BMD, QCT and opportunistic CT (L1 Hounsfield units [HU]) were performed. LS TBS and hip cortical and trabecular parameters were assessed using DXA. Baseline group comparisons were performed by unpaired T-test with change over time evaluated by repeated measures ANOVA.

Results: Participant mean age, BMI, and lowest T-score were 67.0 years, 26.0 kg/m, and -2.7; no between-group differences in serum chemistries, 25(OH)D, or BMD were observed. LS-BMD increased (p<0.001) with TPD or TPD/RLX as measured by DXA (4.8%/5.2%), QCT (13%/9.4%), or HU (15.6%/10.2%) with no between-group difference. TPD/RLX produced beneficial between-group differences in total proximal femur BMD (1.5%, p<0.05) and cortical thickness (1.6%, p<0.05).

Conclusion: Compared with daily TPD, cyclic TPD/RLX comparably increased spine BMD and might have favorable effects on proximal femur BMD and cortical thickness.
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http://dx.doi.org/10.1007/s11657-021-00933-6DOI Listing
April 2021

Opportunistic use of dual-energy X-ray absorptiometry to evaluate lumbar scoliosis.

Arch Osteoporos 2021 02 23;16(1):38. Epub 2021 Feb 23.

Department of Orthopedics and Rehabilitation, Medical Foundation Centennial Building, University of Wisconsin, 1685 Highland Ave, 6th floor, Madison, WI, 53705-2281, USA.

Low bone mineral density is associated with spinal deformity. Dual-energy X-ray absorptiometry (DXA), a modality that assesses bone density, portends a theoretical means to also assess spinal deformity. We found that DXA can reliably assess spine alignment. DXA may permit surveillance of spine alignment, i.e., scoliosis in the clinical setting.

Purpose: Osteoporosis and scoliosis are interrelated disease processes. Dual-energy X-ray absorptiometry (DXA), used to assess bone density, can also be used to evaluate spinal deformity since it captures a posteroanterior (PA) image of the lumbar spine. We assessed the use of DXA to evaluate lumbar spine alignment.

Methods: A lumbar spine DXA phantom was used to assess the effects of axial and sagittal plane rotation on lumbar bone mineral content (BMC), density (BMD), and L1-L4 Cobb angle measurements. Using two subject cohorts, intra- and inter-observer reliability and validity of using DXA for L1-L4 Cobb angle measurements in the coronal and sagittal planes were assessed.

Results: Axial and sagittal plane rotation greater than 15° and 10°, respectively, significantly reduced measured BMD and BMC; there was minimal effect on Cobb angle measurement reliability. In human subjects, excellent intra- and inter-observer reliability was observed using lumbar PA DXA images for Cobb angle measurements. Agreement between Cobb angles derived from lumbar PA DXA images and AP lumbar radiographs ranged from good to excellent. The mean difference in Cobb angles between supine lumbar PA DXA images and upright AP lumbar radiographs was 2.8° in all subjects and 5.8° in those with scoliosis.

Conclusions: Lumbar spine rotation does not significantly affect BMD and BMC within 15° and 10° of axial and sagittal plane rotation, respectively, and minimally affects Cobb angle measurement. Spine alignment in the coronal plane can be reliably assessed using lumbar PA DXA images.
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http://dx.doi.org/10.1007/s11657-021-00898-6DOI Listing
February 2021

Controversies in Vitamin D: A Statement From the Third International Conference.

JBMR Plus 2020 Dec 10;4(12):e10417. Epub 2020 Nov 10.

Department of Medicine, Endocrinology Division, College of Physicians and Surgeons Columbia University New York NY USA.

The Third International Conference on Controversies in Vitamin D was held in Gubbio, Italy, September 10-13, 2019. The conference was held as a follow-up to previous meetings held in 2017 and 2018 to address topics of controversy in vitamin D research. The specific topics were selected by the steering committee of the conference and based upon areas that remain controversial from the preceding conferences. Other topics were selected anew that reflect specific topics that have surfaced since the last international conference. Consensus was achieved after formal presentations and open discussions among experts. As will be detailed in this article, consensus was achieved with regard to the following: the importance and prevalence of nutritional rickets, amounts of vitamin D that are typically generated by sun exposure, worldwide prevalence of vitamin D deficiency, the importance of circulating concentrations of 25OHD as the best index of vitamin D stores, definitions and thresholds of vitamin D deficiency, and efficacy of vitamin D analogues in the treatment of psoriasis. Areas of uncertainly and controversy include the following: daily doses of vitamin D needed to maintain a normal level of 25OHD in the general population, recommendations for supplementation in patients with metabolic bone diseases, cutaneous production of vitamin D by UVB exposure, hepatic regulation of 25OHD metabolites, definition of vitamin D excess, vitamin D deficiency in acute illness, vitamin D requirements during reproduction, potential for a broad spectrum of cellular and organ activities under the influence of the vitamin D receptor, and potential links between vitamin D and major human diseases. With specific regard to the latter area, the proceedings of the conference led to recommendations for areas in need of further investigation through appropriately designed intervention trials. © 2020 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745884PMC
December 2020

A probable atypical ulnar fracture in a man receiving denosumab.

Bone 2021 Feb 29;143:115726. Epub 2020 Oct 29.

University of Wisconsin, Madison, WI, USA.

Background: Atypical femur fractures are widely recognized and associated with anti-resorptive therapy, most commonly bisphosphonates. These fractures generally occur in the femoral shaft or subtrochanteric region. Cases of atypical fractures at non-femur sites, including the ulna, have been reported.

Case Report: Here we report a probable atypical ulnar fracture in a man receiving denosumab, who had been using his upper extremities for transfers and ambulation. Radiographs demonstrated a non-comminuted, transverse fracture somewhat similar to findings of atypical femur fractures. He was deemed a poor surgical candidate and treated with teriparatide. To our knowledge, this is the first reported probable atypical ulnar fracture potentially associated with denosumab use.

Conclusion: We believe it important that clinicians be aware of the association of anti-resorptive therapy with atypical fractures not only of the femur, but also at other skeletal sites. In patients on long-term anti-resorptive therapy, it is appropriate to consider that persistent "prodromal" pain might indicate an impending atypical fracture at an atypical skeletal site.
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http://dx.doi.org/10.1016/j.bone.2020.115726DOI Listing
February 2021

Comparison of screening tools for optimizing fracture prevention in Canada.

Arch Osteoporos 2020 10 27;15(1):170. Epub 2020 Oct 27.

University of Wisconsin, Madison, WI, USA.

The best screening strategy to identify treatment qualification based upon indicators of high fracture risk (low-trauma fractures of the hip, spine, or multiple fracture episodes at other sites; high fracture probability with the Canadian fracture risk assessment [FRAX®] tool major osteoporotic fracture [MOF] computed with bone mineral density [BMD] > 20%; or vertebral fracture on vertebral fracture assessment [VFA]) was FRAX-MOF without BMD using a cutoff of ≥ 10%.

Purpose: To inform clinical practice guidelines in Canada, we compared multiple screening tools using the population-based Manitoba BMD Program registry.

Methods: The study populations consisted of (a) 28,906 individuals > 50 years or older, and (b) 15,429 women age > 65 years undergoing baseline BMD assessment (2010-2018). We considered two treatment qualifications: Treatment Approach 1: prior high-risk fracture, high fracture probability (FRAX-MOF with BMD > 20%), or vertebral fracture on VFA; Treatment Approach 2: Approach 1 or an osteoporotic BMD T score. Candidate screening tools were FRAX-MOF without BMD, age alone, weight alone, SCORE, ORAI, SOFSURF, OSIRIS, ABONE, and OST. Healthcare records were assessed for the presence of incident fracture diagnoses.

Results: Among all individuals, FRAX-MOF without BMD demonstrated the best ability to identify those satisfying Treatment Approach 1 (area under the curve [AUC 0.863]) and was significantly better than all other screening tools (P < 0.001). For identification of individuals satisfying Treatment Approach 2, FRAX-MOF without BMD showed moderate stratification (AUC 0.735), slightly lower than OSIRIS (AUC 0.752, P < 0.05), similar to SCORE (AUC 0.739, P > 0.05) and significantly better than all other screening tools (P < 0.05). For prediction of incident MOF, FRAX-MOF without BMD achieved the highest performance (AUC 0.652), and was significantly better than all other screening tools except OSIRIS. AUCs among women age > 65 years tended to be greater with a similar ranking, and no tool outperformed FRAX-MOF without BMD. Based upon a summary score, the highest ranked strategy was FRAX-MOF without BMD using a cutoff of 10%.

Conclusions: All screening tools show some ability to identify individuals qualifying for treatment and stratify risk for incident fracture. For treatment based upon indicators of high fracture risk, the best performing strategy was FRAX-MOF without BMD using a cutoff of ≥ 10%.
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http://dx.doi.org/10.1007/s11657-020-00846-wDOI Listing
October 2020

MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19.

Eur J Endocrinol 2020 Nov;183(5):R133-R147

Institute of Endocrine and Metabolic Sciences, San Raffaele, Vita-Salute University and IRCCS Hospital, Milano, Italy.

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.
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http://dx.doi.org/10.1530/EJE-20-0665DOI Listing
November 2020

Preoperative bone health assessment and optimization in spine surgery.

Neurosurg Focus 2020 08;49(2):E2

2University of Wisconsin School of Medicine and Public Health, Osteoporosis Clinical Research Program, Madison, Wisconsin.

Objective: The purpose of this investigation was to characterize the bone health in preoperative spine surgery patients. This information will provide a framework to understand the needs and methods for providing bone health optimization in elective spine surgery patients.

Methods: A retrospective study of 104 patients undergoing bone health optimization was performed. Patients were selected based on risk factors identified by the surgeon and suspected compromised bone health. Evaluation included history and examination, laboratory investigations, and bone mineral density (BMD) at 3 sites (femoral neck, lumbar spine, and radius). Patients' bone status was classified using WHO criteria and expanded criteria recommended by the National Osteoporosis Foundation (NOF). The 10-year Fracture Risk Assessment Tool (FRAX) scores of the hip and major osteoporotic fracture (MOF) were calculated with and without femoral neck BMD, with spine BMD, and with the trabecular bone score (TBS). Antiresorptive and anabolic agents were provided in accordance with meeting NOF criteria for treatment of osteoporosis.

Results: The mean patient age was 69.0 years, and 81% of patients were female. The mean historical height loss was 5.6 cm, and 54% of patients had a history of fracture. Secondary osteoporosis due to chronic renal failure, inflammatory arthritis, diabetes, and steroid use was common (51%). The mean 25-hydroxy vitamin D was 42.4 ng/ml and was normal in 81% of patients, with only 4 patients being deficient. The mean T-scores were -2.09 (SD 0.71) of the femoral neck, -0.54 (1.71) of the lumbar spine, and -1.65 (1.38) of the distal radius. These were significantly different. The 10-year FRAX MOF score was 20.7%, and that for hip fracture was 6.9% using the femoral neck BMD and was not significantly different without the use of BMD. The FRAX risk-adjusted score using the lumbar spine BMD and TBS was significantly lower than that for the hip. Osteoporosis was present in 32.1% according to WHO criteria compared with 81.6% according to NOF criteria. Antiresorptive medications were recommended in 31 patients and anabolic medications in 44 patients.

Conclusions: Surgeons can reliably identify patients with poor bone health by using simple criteria, including historical height loss, history of fracture, comorbidities associated with osteoporosis, analysis of available imaging, and calculation of FRAX score without BMD. High-risk patients should have BMD testing and bone health assessment. In patients with osteoporosis, a comprehensive preoperative bone health assessment is recommended and, if warranted, pharmacological treatment should be started.
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http://dx.doi.org/10.3171/2020.5.FOCUS20255DOI Listing
August 2020

A Newly Recognized DXA Confounder: The Potassium-Binding Medication Sodium Zirconium Cyclosilicate.

J Clin Densitom 2020 May 21. Epub 2020 May 21.

University of Wisconsin-Madison, Madison, WI, USA. Electronic address:

Objective: Radio-dense artifacts, including contrast material, alter dual-energy X-ray absorptiometry (DXA) results. An apparent diffuse artifact was identified during spine DXA acquisition in a patient without recent radiographic procedures. The patient reported taking sodium zirconium cyclosilicate (SZC; Lokelma®) 10 g 1 h before scanning. SZC is a potassium-binding agent recently marketed to treat hyperkalemia. Given the chemical composition, we hypothesized that SZC may alter DXA results. This study evaluated if SZC affects DXA results using an encapsulated spine and a total body phantom.

Methodology: An encapsulated spine and total body phantom were scanned using a Lunar iDXA. Each phantom was scanned 5 times serially without repositioning in 5 configurations: (1) Bare, (2) 45 mL tap water, (3) 90 mL water, (4) 10 g SZC in 45 mL of water, and (5) 30 g SZC in 90 mL of water. Water and SZC was contained in plastic quart bags, folded, and placed over L2-3 on the spine phantom and flat over the pelvis/torso of the total body phantom.

Results: Tap water did not change spine phantom measurements, but did increase (p < 0.05) total body phantom lean mass 46 g and 89 g with 45 mL and 90 mL, respectively. SZC 10 g or 30 g increased (p < 0.001) L2 and L3 bone mineral density (BMD) 18%-110%, mean 0.295 and 0.924 g/cm, respectively, while L1 and L4 BMD was statistically, but not clinically, altered by <0.010 g/cm. A dose-dependent change (p < 0.001) in total body phantom trunk measurements was demonstrated. The 10 g dose increased lean mass 16.8% and BMC 1%; fat mass was reduced 16.6%, while 30 g increased lean 41.9%, BMC 3.2%, and decreased fat 42.9%.

Conclusion: SZC confounds BMD and body composition phantom measurements. It is likely that SZC alters DXA results in humans. DXA technologists and interpreters should be aware of this confounder.
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http://dx.doi.org/10.1016/j.jocd.2020.05.008DOI Listing
May 2020

Osteoporosis treatment considerations based upon fracture history, fracture risk assessment, vertebral fracture assessment, and bone density in Canada.

Arch Osteoporos 2020 06 23;15(1):93. Epub 2020 Jun 23.

University of Wisconsin, Madison, WI, USA.

Among 39,475 women, age 65 years and older, use of fracture history, major osteoporotic fracture (MOF) probability from FRAX®, vertebral fracture assessment (VFA), and bone mineral density (BMD) T-score stratified women into different levels of risk. The majority of women identified as being at high risk from fracture history, FRAX MOF-BMD > 20%, or vertebral fracture on VFA had a BMD T-score in the osteoporotic range.

Purpose: To inform criteria for pharmacologic treatment in women age 65 years and older, we examined subgroups defined from fracture history, MOF calculated with BMD (MOF-BMD), VFA, and BMD T-score using the population-based Manitoba BMD Program registry.

Methods: The study population consisted of women age > 65 years was divided into mutually exclusive subgroups based upon fracture history, MOF-BMD ≥ 20%, vertebral fracture on VFA, and osteoporotic BMD T-score. Healthcare records were assessed for the presence of fracture diagnosis codes occurring after DXA assessment. For each subgroup, we estimated the proportion of individuals with BMD T-score in the osteoporotic range, predicted versus observed 10-year MOF probability, hazard ratio (HR) for MOF, and number needed to treat (NNT) for 3 years to prevent a fracture event.

Results: The study population consisted of 39,475 women (median age 72 years). The majority of women (76.8%) selected as being at high risk based on fracture history, MOF-BMD > 20%, or vertebral fracture on VFA had a BMD T-score in the osteoporotic range. During a median follow-up of 8 years, 5169 (13.1%) sustained one or more incident MOF. Fracture rates and HRs generally paralleled the FRAX prediction, except in women with a positive VFA where predicted risk based upon clinical risk factors prior to VFA underestimated the observed risk. NNT differed by the risk subgroup, and showed a gradient of decreasing NNT (consistent with greater benefit) in individuals with the highest fracture risk.

Conclusions: Fracture history, fracture probability from FRAX, targeted vertebral fracture assessment (VFA), and BMD T-score can stratify older women into different levels of risk and treatment benefit. These results are expected to inform clinical practice guidelines in Canada.
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http://dx.doi.org/10.1007/s11657-020-00775-8DOI Listing
June 2020

Impact of spine-hip discordance on fracture risk assessment and treatment qualification in Canada: the Manitoba BMD registry.

Arch Osteoporos 2020 06 8;15(1):85. Epub 2020 Jun 8.

University of Wisconsin, Madison, WI, USA.

In 50,330 women undergoing bone mineral density (BMD) testing, adjusting FRAX® major osteoporotic fracture (MOF) probability for T-score differences between lumbar spine and femoral neck had a small impact on treatment qualification, with only 1.1% reclassified from below to above the 20% MOF intervention threshold.

Purpose: Discordance between lumbar spine and femoral neck T-score measurements are frequently encountered in clinical practice. The FRAX tool accepts femoral neck BMD as an optional input but does not consider lumbar spine BMD, though adjustments based upon T-score difference have been proposed. This analysis was undertaken to examine change in treatment qualification using the lumbar spine T-score adjustment to FRAX assuming an intervention threshold of 20% MOF.

Methods: Women aged > 50 years with baseline FRAX MOF probability computed with femoral neck BMD of ≥ 20% but without previous high-risk fracture or high-risk medication use were identified in the province of Manitoba BMD registry. If lumbar spine T-score was lower than the femoral neck T-score, MOF probability was recalculated, and treatment qualification, reassessed.

Results: The study population consisted of 50,300 women (mean age 64.2 ± 8.6 years). During mean follow-up of 9.5 years, 4550 sustained incident MOF. The baseline mean T-score difference (femoral neck minus lumbar spine) was - 0.2 ± 1.1. Recalculated MOF probability using the T-score difference significantly improved overall net reclassification index for incident MOF prediction (+ 0.017, p < 0.001). A total of 561 (1.1%) of these women were reclassified from below to above 20% MOF probability based upon the T-score difference. No individuals with MOF probability less than 15% were reclassified to the higher risk category. Risk reclassification increased with lower lumbar spine T-score (15.6% reclassification for lumbar spine T-score of - 3.5 or lower, 4.0% of the study population) and larger T-score differences (9.7% reclassification for T-score difference of 2.5 or more, < 1% of the study population).

Conclusions: Very few women showed risk reclassification based upon adjusting FRAX MOF probability for lumbar spine T-score. Reclassification occurred only in those with baseline MOF probability > 15%.
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http://dx.doi.org/10.1007/s11657-020-00763-yDOI Listing
June 2020

"Effect of very dense artifacts on Hologic and general electric bone densitometry results".

Arch Osteoporos 2020 05 21;15(1):77. Epub 2020 May 21.

Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.

Very dense artifacts confound bone density measurement. Hologic and GE densitometers exclude artifact density and GE also excludes associated area. Consequently, BMD is decreased with Hologic software. Despite different manufacturers' approaches, when dense artifacts overlay the spine, the affected vertebral body should be excluded from the reported BMD.

Purpose: Very dense objects, such as lead bullets are described as "black hole" artifacts on Hologic densitometers. Whether similar results occur on GE scanners is not reported. We hypothesized that dense artifacts confound both brands of densitometers.

Methods: Three lead bullets of varying size were placed overlying or adjacent to L3 on anthropomorphic and encapsulated aluminum spine phantoms. Three scans were acquired with and without projectiles on a Hologic Discovery W, GE iDXA, and Prodigy densitometer.

Results: Lead bullets are measured as having high bone mineral content (BMC); they appear black in dual-energy mode on Hologic scanners and are colored blue on GE scanners. On Hologic scanners, BMC of a dense artifact over bone is excluded, but the bone area is not altered. Consequently, bone mineral density (BMD) of the affected vertebra, and of L1-4, is decreased. For example, a .45 caliber bullet over L3 decreased BMD (p < 0.05) by 48.3% and L1-4 by 9.1%. GE scanners excluded associated BMC and area covered by the artifact, thereby minimizing impact on BMD. Dense artifacts over soft tissue on a phantom do not substantially affect BMD on either manufacturer's densitometer when scanned.

Conclusion: Densitometer manufacturers handle very dense artifacts differently. GE software removes artifact BMC and area with resultant minimal impact on BMD, Hologic removes only BMC, not area, thereby decreasing BMD. Regardless of this difference, when dense artifacts overlay the spine, it is best to exclude the affected vertebral body. Finally, the BMD stability observed with artifacts over soft tissue may not be replicated in humans.
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http://dx.doi.org/10.1007/s11657-020-00742-3DOI Listing
May 2020

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS- 2020 UPDATE .

Endocr Pract 2020 May;26(5):564-570

The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options. This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis.
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http://dx.doi.org/10.4158/GL-2020-0524DOI Listing
May 2020

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS-2020 UPDATE.

Endocr Pract 2020 May;26(Suppl 1):1-46

The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options. This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis. = 25-hydroxyvitamin D; = American Association of Clinical Endocrinologists; = American College of Endocrinology; = atypical femoral fracture; = American Society for Bone and Mineral Research; = best evidence level; = bone mineral density; = bone turnover marker; = confidence interval; = clinical practice guideline; = C-terminal telopeptide type-I collagen; = dual-energy X-ray absorptiometry; = evidence level; = U.S. Food and Drug Administration; = Fracture Risk Assessment Tool; = gastrointestinal; = Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly Pivotal Fracture Trial (zoledronic acid and zoledronate are equivalent terms); = International Society for Clinical Densitometry; = international units; = intravenous; = least significant change; = National Osteoporosis Foundation; = osteonecrosis of the jaw; = serum amino-terminal propeptide of type-I collagen; = parathyroid hormone; = recommendation; = region of interest; = relative risk; = standard deviation; = trabecular bone score; = vertebral fracture assessment; = World Health Organization.
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http://dx.doi.org/10.4158/GL-2020-0524SUPPLDOI Listing
May 2020

Do patients that fracture with normal DXA-measured BMD have normal bone?

Arch Osteoporos 2020 05 11;15(1):70. Epub 2020 May 11.

University of Wisconsin School of Medicine and Public Health, UW Health, 2870 University Avenue, Suite 100, Madison, WI, 53705, USA.

Patients that sustain "osteoporosis-related" fractures may have normal BMD at the hips and spine, but rarely have normal bone when other clinically available studies are considered. Such data often exist and can inform clinical decisions regarding osteoporosis therapy.

Purpose: Dual-energy X-ray absorptiometry (DXA) measured bone mineral density (BMD) at the hip and spine is widely used to diagnose osteoporosis. However, patients that sustain "osteoporosis-related" fractures often have normal BMD at these sites. The aim of this study was to explore whether older adults with fracture, but normal reported hip and spine BMD, also have normal bone using additional clinically available assessments.

Methods: This retrospective electronic medical record study included 387 patients evaluated by a university-based fracture liaison service with spine and hip DXA; 32 (8.3%) had normal spine/hip BMD reported. In this cohort, clinically available bone data including 0.3 and ultradistal radius T-scores, trochanteric T-scores, lumbar spine trabecular bone score (TBS), L1 opportunistic CT Hounsfield units (HU), and femoral cortical index (FCI) were assessed.

Results: One or more of the above noted studies were available in 30/32 patients. UD and 0.3 radius results were available in 21 patients, and 18 (85.7%) had T-scores < - 1.0. Trochanteric values were available in 16; T-scores were < - 1.0 in 18.8%. TBS data were available in 24; partially degraded or degraded values were present in 41.7%. L1 opportunistic CT was available in 25 patients, 80% were below normal, and < 150 HU. Finally, femoral cortical index (FCI) was measurable in 9 subjects; 66.7% were below < 0.4. When including all additional available data in the skeletal assessment, only 5/387 (1.3%) were identified with normal bone.

Conclusion: Patients with normal spine/hip BMD who sustain fracture rarely have normal bone when all available data are considered.
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http://dx.doi.org/10.1007/s11657-020-00745-0DOI Listing
May 2020

Targeted vertebral fracture assessment for optimizing fracture prevention in Canada.

Arch Osteoporos 2020 05 3;15(1):65. Epub 2020 May 3.

University of Wisconsin, Madison, WI, USA.

Vertebral fracture assessment (VFA) provides incremental information in identifying women and men aged 70 years and older qualifying for anti-osteoporosis treatment compared with FRAX major osteoporotic fracture (MOF) probability computed with bone mineral density (BMD).

Purpose: This analysis was performed to inform appropriate use of VFA testing as part of Osteoporosis Canada's Guidelines Update, assuming vertebral fracture is an indication for pharmacotherapy in women and men.

Methods: Women and men aged 70 years and older without previous high-risk fracture (i.e., hip, spine, or multiple fractures) were identified in a BMD registry for the province of Manitoba, Canada. MOF probability with BMD was computed using the Canadian FRAX tool. VFA was performed in those with a minimum BMD T-score of -1.5 or lower.

Results: The study population consisted of 7289 women (mean age 76.7 ± 5.6 years) and 1323 men (77.9 ± 5.8 years). More women than men qualified for VFA testing (48.7% vs 25.4%, respectively, p < 0.001). Among those undergoing VFA, a vertebral fracture was more commonly detected among men than women (22.9% vs 13.3%, p < 0.001), and vertebral fracture prevalence increased with lower BMD T-score (both p trend <0.001). The number needed to screen with VFA to detect a vertebral fracture was 8 for women and 4 for men. MOF probability was substantially lower in men than in women, and fewer men than women (3.3% vs 20.2%, p < 0.001) met a treatment threshold of MOF 20% or greater. In those with MOF probability <20%, VFA identified an incremental 5.4% of men and 3.4% of women for treatment based upon vertebral fracture.

Conclusions: The number needed to screen to identify a previously unappreciated vertebral fracture is low and further improves with lower BMD T-score. VFA identified more men as qualifying for treatment than MOF probability. In women, treatment qualification was predominantly from MOF probability.
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http://dx.doi.org/10.1007/s11657-020-00735-2DOI Listing
May 2020

Trends in Hip Fracture Mortality in Wisconsin and the United States, 1999-2017.

WMJ 2020 Mar;119(1):48-51

University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Introduction: Hip fracture affects >300,000 Americans each year, and the mortality rate following these fractures is high.

Methods: Authors searched the Centers for Disease Control and Prevention Wide-Ranging Online Database for Epidemiologic Research (WONDER) for incidences of hip fracture as a contributing cause of death and stratified by sex, age, race, ethnicity, state, month of death, and underlying cause of death across the United States and Wisconsin.

Results: Wisconsin has the third-highest age-adjusted death rate for hip fracture in the United States. Those who die from hip fracture are most likely to do so in a nursing home. Hip fracture deaths occur more frequently between October and March and often are associated with respiratory illness.

Conclusion: Hip fracture is a major contributing cause of death. Wisconsin residents are particularly affected by this risk.
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March 2020

Favorable skeletal benefit/risk of long-term denosumab therapy: A virtual-twin analysis of fractures prevented relative to skeletal safety events observed.

Bone 2020 05 21;134:115287. Epub 2020 Feb 21.

University of Wisconsin-Madison, Madison, WI, USA.

Antiresorptive therapies reduce fracture risk; however, long-term bone turnover inhibition may raise concerns about rare, but serious, skeletal adverse events-atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). Denosumab, a fully human monoclonal antibody against RANKL, has demonstrated sustained low vertebral and nonvertebral fracture rates with low skeletal adverse event rates in the 3-year FREEDOM trial and its 7-year Extension (in which all subjects received open-label denosumab). In this analysis, we aimed to estimate fractures prevented relative to skeletal adverse events observed with 10 years of denosumab therapy. We modeled a hypothetical placebo group using the virtual-twin method, thereby allowing calculation of fractures prevented with denosumab treatment (relative to the virtual-placebo group) in the context of AFF or ONJ events observed in the long-term denosumab group. Estimated virtual-placebo and observed long-term denosumab exposure-adjusted fracture rates per 100,000 subject-years were calculated for fractures classified as clinical (3180 and 1777, respectively), major osteoporotic (2699 and 1525), vertebral (1879 and 901), and nonvertebral (2924 and 1528), and compared with observed AFF and ONJ in the long-term denosumab group (5 and 35 per 100,000 subject-years, respectively). The skeletal benefit/risk ratio (fractures prevented per adverse event observed) for clinical fractures was 281 (AFF) and 40 (ONJ). Based on this model, denosumab treatment for up to 10 years has a favorable skeletal benefit/risk profile when comparing fractures prevented per skeletal adverse event observed. Clinical trial registration: NCT00089791, NCT00523341.
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http://dx.doi.org/10.1016/j.bone.2020.115287DOI Listing
May 2020

Bone Health Optimization in Orthopaedic Surgery.

J Bone Joint Surg Am 2020 Apr;102(7):574-581

Department of Orthopedics & Rehabilitation (A.K., K.J.H., and P.A.A.), and the Osteoporosis Clinical Research Program (N.B.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Background: Osteoporosis is associated with adverse orthopaedic surgical outcomes. Bone health optimization is a preoperative intervention intended to reduce the likelihood of postoperative complications. We aimed to characterize a patient cohort referred for bone health optimization to test the hypothesis that poor bone quality is common in orthopaedic surgery and that many such patients meet guidelines for osteoporosis treatment.

Methods: This retrospective study evaluated 124 patients referred for bone health optimization who were ≥50 years of age and candidates for arthroplasty or thoracolumbar surgery. The Fracture Risk Assessment Tool (FRAX) risk factors and dual x-ray absorptiometry (DXA) results were collected. When available, opportunistic computed tomographic (CT) imaging and the trabecular bone score were evaluated. The World Health Organization (WHO) diagnostic and National Osteoporosis Foundation (NOF) treatment guidelines were applied.

Results: All patients were referred by their orthopaedic surgeon; their mean age was 69.2 years, 83% of patients were female, 97% were Caucasian, and 56% had sustained a previous fracture. The mean historical height loss (and standard deviation) was 5.3 ± 3.3 cm for women and 6.0 ± 3.6 cm for men. The mean lowest T-score of the hip, spine, or wrist was -2.43 ± 0.90 points in women and -2.04 ± 0.81 points in men (p < 0.08). Osteoporosis (T-score of ≤-2.5 points) was present in 45% of women and 20% of men; only 3% of women and 10% of men had normal bone mineral density. Opportunistic CT scans identified 60% of patients as likely having osteoporosis. The trabecular bone score identified 34% of patients with degraded bone microarchitecture and 30% of patients with partially degraded bone microarchitecture. The NOF threshold for osteoporosis treatment was met in 91% of patients. Treatment was prescribed in 75% of patients (45% anabolic therapy and 30% antiresorptive therapy).

Conclusions: Osteoporosis, degraded bone microarchitecture, prior fracture, and elevated fracture risk were common. Given the high prevalence of impaired bone health in this cohort, we believe that bone health screening, including FRAX assessment, should be considered in selected patients undergoing orthopaedic surgery as part of the preoperative optimization for all adults who are ≥50 years of age.

Level Of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.19.00999DOI Listing
April 2020

Comparison of treatment strategies and thresholds for optimizing fracture prevention in Canada: a simulation analysis.

Arch Osteoporos 2019 12 19;15(1). Epub 2019 Dec 19.

University of Wisconsin, Madison, USA.

This comparison of osteoporosis treatment strategies and intervention thresholds highlights tradeoffs in terms of number of individuals qualifying for treatment and estimated fractures prevented.

Purpose: The current analysis was performed to inform the following key question as part of the Osteoporosis Canada's Osteoporosis Guidelines Update: "What is the best strategy to identify those at high fracture risk for pharmacotherapy in order to prevent the most fractures, considering both population and patient perspectives?"

Methods: The study population consisted of 66,878 women age 50 years and older (mean age 66.0 ± 9.7 years) with documented fracture probability assessment (FRAX) and fracture outcomes. Fractures over the next 5 years were identified through linked administrative healthcare data. We estimated the fraction of the population that would warrant treatment and the number of fractures avoided per 1000 person-years according to multiple strategies and thresholds. Strategies were then rank ordered using 19 metrics.

Results: During mean 4.4 years, 863 (3.5%) sustained one or more major osteoporotic fractures (MOF), 212 (0.8%) sustained a hip fracture, and 1210 (4.9%) sustained any incident fracture. For woman age 50-64 years, the highest ranked strategy was treatment based upon total hip T score ≤ -2.5, but several other strategies fell within 0.5 overall ranking. For women age 65 years and older, MOF > 20% was the highest ranked strategy with no closely ranked strategies. Pooling both age subgroups gave MOF > 20% as the highest ranked strategy, with several other strategies within 0.5 overall ranking.

Conclusions: Choice of treatment strategy and threshold for osteoporosis management strongly influences the number of individuals for whom pharmacologic treatment would be recommended and on estimated fracture rates in the population. This evidence-based approach to comparing these strategies will help to inform guidelines development in Canada and may be on interest elsewhere.
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http://dx.doi.org/10.1007/s11657-019-0660-8DOI Listing
December 2019

Semi-Recumbent Vibration Exercise in Older Adults: A Pilot Study of Methodology, Feasibility, and Safety.

Gerontol Geriatr Med 2019 Jan-Dec;5:2333721419881552. Epub 2019 Oct 16.

Osteoporosis Clinical Research Program, University of Wisconsin-Madison, USA.

Objectives: Older adults with impaired physical function are at risk for further functional decline in part due to limited ability to engage in regular exercise. Effective approaches to exercise in this vulnerable population are needed to improve functional capacity and optimize independence.

Methods: Thirty-two residential care apartment complex (RCAC) residents, age ≥70, with low short physical performance battery (SPPB) scores were recruited and randomly assigned to a crossover-design study exploring feasibility and safety of semi-recumbent vibration exercise in older adults living in one RCAC. The primary outcomes were retention and adherence rates and adverse events.

Results: The retention rate was 78%. Adherence rate was 79.7% and 78.6% during the vibration and control training sessions, respectively. Thirty-eight adverse events (AEs) occurred. Mild muscle soreness and knee pain were the only AEs related to vibration exercise. No serious adverse events (SAEs) were study-related. Participants were able to increase training intensity and load and rated the training enjoyable.

Conclusion: Semi-recumbent vibration exercise was feasible, well tolerated, and safe in RCAC residents with reduced physical function. Future studies need to examine the effect of this type of exercise on physical function, mobility, falls, and quality of life.
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http://dx.doi.org/10.1177/2333721419881552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796212PMC
October 2019

Bone Health Optimization: Beyond Own the Bone: AOA Critical Issues.

J Bone Joint Surg Am 2019 Aug;101(15):1413-1419

University of Wisconsin Osteoporosis Clinical Research Program, Madison, Wisconsin.

Worldwide, osteoporosis management is in crisis because of inadequate delivery of care, competing guidelines, and confusing recommendations. Additionally, patients are not readily accepting the diagnosis of poor bone health and often are noncompliant with treatment recommendations. Secondary fracture prevention, through a program such as Own the Bone, has improved the diagnosis and medical management after a fragility fracture. In patients who undergo elective orthopaedic procedures, osteoporosis is common and adversely affects outcomes. Bone health optimization is the process of bone status assessment, identification and correction of metabolic deficits, and initiation of treatment, when appropriate, for skeletal structural deficits. The principles of bone health optimization are similar to those of secondary fracture prevention and can be initiated by all orthopaedic surgeons. Patients who are ≥50 years of age should be assessed for osteoporosis risk and, if they are in a high-risk group, bone density should be measured. All patients should be counseled to consume adequate vitamin D and calcium and to discontinue use of any toxins (e.g., tobacco products and excessive alcohol consumption). Patients who meet the criteria for pharmaceutical therapy for osteoporosis should consider delaying surgery for a minimum of 3 months, if feasible, and begin medication treatment. Orthopaedic surgeons need to assume a greater role in the care of bone health for our patients.
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http://dx.doi.org/10.2106/JBJS.18.01229DOI Listing
August 2019

Dual-Energy X-Ray Absorptiometry Body Composition in NCAA Division I Athletes: Exploration of Mass Distribution.

Sports Health 2019 Sep/Oct;11(5):453-460. Epub 2019 Jul 26.

University of Wisconsin Badger Athletic Performance Program, Madison, Wisconsin.

Background: Body composition assessment is frequently used in sports medicine and athletic performance environments to assess change in response to strength training and nutrition programs. However, to effectively do so requires knowledge regarding expected body composition values relative to sport and sex. Dual-energy x-ray absorptiometry (DXA) is widely used to evaluate body composition, although its utility in relationship to specific sports, performance, or rehabilitation is not clearly defined.

Hypothesis: Body composition metrics and distribution of National Collegiate Athletic Association Division I collegiate athletes will vary based on sport and sex.

Level Of Evidence: Level 4.

Study Design: Cross-sectional study.

Methods: A convenience sample of 337 athletes (229 men and 108 women) participating in football, wrestling, soccer, hockey, basketball, golf, softball, or volleyball was evaluated. DXA-measured total body composition, including bone mineral density (BMD), % lean mass, % fat, and regional distribution, were compared by sex, sport, and with an age-matched National Health and Nutrition Examination Survey (NHANES) population.

Results: Men had higher BMD, lower % fat (16.4% vs 25.2%) and higher % lean mass (79.2% vs 70.6%) ( < 0.001). Regional composition varied by sport and sex, with women having a greater proportion of lean mass at the trunk and men in their arms ( < 0.0001). Leg lean mass was distributed similarly between sexes (35%). Overall, the normative group (NHANES) had lower BMD and higher percentage fat.

Conclusion: DXA-measured body composition and lean mass distribution varies by sport and sex in Division I athletes. The observed difference to the NHANES population emphasizes challenges in identifying appropriate comparison populations, reinforcing the need to compare athletes with their own baseline.

Clinical Relevance: These findings establish a framework to investigate the relevance of these variances and determine the utility of body composition analysis in elite athletes.
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http://dx.doi.org/10.1177/1941738119861572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745817PMC
November 2019

Unrecognized Osteoporosis Is Common in Patients With a Well-Functioning Total Knee Arthroplasty.

J Arthroplasty 2019 Oct 30;34(10):2347-2350. Epub 2019 May 30.

Department of Orthopedics & Rehabilitation, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Background: Peri-prosthetic fractures after total knee arthroplasty (TKA) are associated with poorer outcomes and high costs. We hypothesize that osteoporosis is under-recognized in the TKA population. The purpose of this study is to report osteoporosis prevalence in a healthy cohort of patients with well-functioning TKA and to compare prevalence between males and females.

Methods: This study is a cross-sectional study of 30 adults (15 males/15 females) aged 59-80 years without known bone health issues who volunteered to undergo routine dual-energy X-ray absorptiometry 2-5 years (average 3.2 ± 0.8) after primary unilateral TKA. These data plus clinical risk factors were used to estimate fracture risk via the Fracture Risk Assessment Tool and skeletal status (normal, osteopenic, osteoporotic) was determined based on the World Health Organization definition. The National Osteoporosis Foundation criteria for treatment were applied to all patients.

Results: Six of 30 (20%) patients had T-score ≤ -2.5. Eighteen of 30 (60%) patients had T-score between -1 and -2.5 and 6 (20%) patients had T-score ≥ -1. Five patients with normal or osteopenic bone mineral density (BMD) had occult vertebral fractures. Eleven of 30 (36.7%) patients met National Osteoporosis Foundation criteria for pharmacologic treatment.

Conclusion: The prevalence of occult osteoporosis meeting treatment guidelines after TKA is substantial in this sample (36.7%). BMD and osteoporosis prevalence are similar between men and women. This underappreciated prevalence of osteoporosis may contribute to peri-prosthetic fracture risk. Arthroplasty surgeons and bone health specialists must be aware of post-operative changes in bone density. These data support the further study of post-operative osteoporosis and consideration of routine BMD screening after TKA.

Level Of Evidence: III.
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http://dx.doi.org/10.1016/j.arth.2019.05.041DOI Listing
October 2019

Osteoporosis Is Common and Undertreated Prior to Total Joint Arthroplasty.

J Arthroplasty 2019 07 28;34(7):1347-1353. Epub 2019 Mar 28.

Department of Orthopedics & Rehabilitation, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Background: Osteoporosis is common in total joint arthroplasty (TJA) patients and likely contributes to the increasing incidence of periprosthetic fracture. Despite this, the prevalence of osteoporosis in patients undergoing elective TJA is inadequately studied. We hypothesize that preoperative osteoporosis is underrecognized and undertreated in the TJA population. The purpose of this study is to report preoperative osteoporosis screening rates and prevalence prior to TJA and rates of pharmacologic osteoporosis treatment in the TJA population.

Methods: This is a retrospective case series of 200 consecutive adults (106F, 94M) aged 48-92 years who underwent elective TJA (100 total hip, 100 total knee) at a single tertiary-care center. Charts were retrospectively reviewed to determine preoperative osteoporosis risk factors, prior dual-energy X-ray absorptiometry (DXA) testing, and prior osteoporosis pharmacotherapy. Fracture risk was estimated using the Fracture Risk Assessment Tool and the National Osteoporosis Foundation criteria for screening and treatment were applied to all patients.

Results: One hundred nineteen of 200 patients (59.5%) met criteria for DXA testing. Of these 119, 21 (17.6%) had DXA testing in the 2 years prior to surgery, and 33% had osteoporosis by T-score. Forty-nine patients (24.5%) met National Osteoporosis Foundation criteria for pharmacologic osteoporosis treatment, and 11 of these 49 received a prescription for pharmacotherapy within 6 months before or after surgery.

Conclusion: One quarter of TJA patients meet criteria to receive osteoporosis medications, but only 5% receive therapy preoperatively or postoperatively. This lack of preoperative osteoporosis screening and treatment may contribute to periprosthetic fracture risk.
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http://dx.doi.org/10.1016/j.arth.2019.03.044DOI Listing
July 2019

Letter to the Editor on "Choices, Compromises, and Controversies in Total Knee and Total Hip Arthroplasty Modifiable Risk Factors: What You Need to Know".

J Arthroplasty 2019 05 18;34(5):1037-1039. Epub 2019 Feb 18.

Department of Endocrinology, Metabolism, and Clinical Nutrition, Medical College of Wisconsin, Milwaukee, WI.

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http://dx.doi.org/10.1016/j.arth.2019.02.014DOI Listing
May 2019

Changes in femoral bone mineral density after total knee arthroplasty: a systematic review and meta-analysis.

Arch Osteoporos 2019 02 23;14(1):23. Epub 2019 Feb 23.

Department of Orthopedics and Rehabilitation, University of Wisconsin School of Medicine and Public Health, UWMF Centennial Building, 1685 Highland Avenue, 6th Floor, Madison, WI, 53705, USA.

Background: Bone loss after total knee arthroplasty (TKA) may lead to periprosthetic fractures that are associated with significant costs (morbidity, economic, etc.) and pose a challenge to operative fixation. This meta-analysis quantifies the change in bone mineral density (BMD) of the distal femur after primary TKA.

Methods: A systematic review of six databases was performed by two independent reviewers. Studies that reported bone density after knee arthroplasty were identified and inclusion/exclusion criteria was applied. Data were extracted and analyzed using the Comprehensive Meta-Analysis Software.

Results: Fourteen studies were included in the analysis. The average decrease in BMD was 0.09 [0.05, 0.13], 0.14 [0.08, 0.20], 0.16 [0.10, 0.23], and 0.16 [0.12, 0.20] g/cm at 3, 6, 12, and 24 months, respectively, corresponding to a 9.3%, 13.2%, 15.8%, and 15.4% BMD loss. A high degree of heterogeneity existed between the studies (I > 90% at most time points).

Conclusion: In summary, there is a rapid and significant 15% decrease in BMD in the first 6 months after TKA that is sustained to 24 months. Better understanding regarding how perioperative optimization of bone health may affect BMD loss and the incidence of periprosthetic fracture is essential.

Level Of Evidence: Therapeutic Level II.
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http://dx.doi.org/10.1007/s11657-019-0572-7DOI Listing
February 2019

Treated Osteoporosis Is Still Osteoporosis.

J Bone Miner Res 2019 04 19;34(4):605-606. Epub 2019 Feb 19.

Columbia University College of Physicians and Surgeons, New York, NY, USA.

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http://dx.doi.org/10.1002/jbmr.3671DOI Listing
April 2019

Invasive Oral Procedures and Events in Postmenopausal Women With Osteoporosis Treated With Denosumab for Up to 10 Years.

J Clin Endocrinol Metab 2019 06;104(6):2443-2452

Oregon Osteoporosis Center, Portland, Oregon.

Context: Antiresorptive therapy has been associated with osteonecrosis of the jaw (ONJ), an infrequent but potentially serious adverse event.

Objective: To assess information on invasive oral procedures and events (OPEs)-dental implants, tooth extraction, natural tooth loss, scaling/root planing, and jaw surgery-during the 7-year Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) Extension study and to present details of positively adjudicated ONJ cases.

Design: Randomized, double-blind, placebo-controlled, 3-year trial (FREEDOM) followed by 7 years of open-label denosumab (FREEDOM Extension). At Extension Year 3, women were asked to record their history of invasive OPEs since the start of the Extension to Year 2.5 and oral events in the prior 6 months. The questionnaire was then administered every 6 months until the end of the Extension.

Setting: Multicenter, multinational clinical trial.

Patients: Postmenopausal women with osteoporosis.

Interventions: Subcutaneous denosumab 60 mg or placebo every 6 months for 3 years, then 7 years of open-label denosumab.

Main Outcome Measures: Self-reports of OPEs and adjudicated cases of ONJ.

Results: Of respondents, 45.1% reported at least one invasive OPE. The exposure-adjusted ONJ rate in FREEDOM Extension was 5.2 per 10,000 person-years. ONJ incidence was higher in those reporting an OPE (0.68%) than not (0.05%).

Conclusions: Although invasive OPEs were common in these denosumab-treated women and were associated with an increased ONJ incidence, the overall rate of ONJ was low, and all cases with complete follow-up resolved with treatment.
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http://dx.doi.org/10.1210/jc.2018-01965DOI Listing
June 2019

Non-invasive DXA-derived bone structure assessment of acromegaly patients: a cross-sectional study.

Eur J Endocrinol 2019 Mar;180(3):201-211

Comenius University Faculty of Medicine, 5th Department of Internal Medicine, University Hospital Bratislava, Bratislava, Slovakia.

Introduction Impaired bone microarchitecture is involved in vertebral fracture (VF) development among acromegaly patients. Aim of the study Comparison of DXA-derived bone parameters, areal BMD (aBMD), trabecular bone score (TBS) and 3D-SHAPER parameters in acromegaly patients with healthy controls. Methods This cross-sectional study evaluated acromegaly patients and a control group of healthy subjects. In all subjects, a single measurement of pituitary axis hormone levels, bone turnover markers, aBMD, (total hip (TH) and lumbar spine (LS)), TBS and 3D-SHAPER of the proximal femur region was performed. All subjects underwent DXA assessment of VF using the semiquantitative approach. Results One hundred six patients with acromegaly (mean age 56.6 years, BMI 30.2 kg/m2) and 104 control subjects (mean age 54.06 years, 28.4 BMI kg/m2) were included. After adjustment for weight, LS aBMD, TBS and TH trabecular volumetric BMD (vBMD) remained lower (P = 0.0048, <0.0001 and <0.0001, respectively) while cortical thickness (Cth) at TH and neck remained thicker (P = 0.006) in acromegaly patients compared with controls. The best multivariate model (model 1) discriminating patients with and without acromegaly included TBS, TH trabecular vBMD and TH Cth parameters (all P < 0.05). Twenty-two VFs (13 acromegaly subjects) were recognized. In these subjects after adjustment for age, FN aBMD, TH cortical sBMD and TH cortical vBMD remained significantly associated with the prevalent VF (OR = 2.69 (1.07-6.78), 2.84 (1.24-6.51) and 2.38 (1.11-5.10) for neck aBMD, TH cortical sBMD and TH cortical vBMD respectively)). The AUCs were similar for each parameter in this model. Conclusions Acromegaly patients, regardless of VF presence, have lower trabecular bone quantitative parameters, but those with VFs had decreased cortical density.
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http://dx.doi.org/10.1530/EJE-18-0881DOI Listing
March 2019

Comparison of vitamin D metabolites in wild and captive baboons.

Am J Primatol 2018 12;80(12):e22935

Department of Neuroscience, Washington University School of Medicine, Saint Louis, Missouri.

Vitamin D adequacy is essential for multiple physiologic processes. With limited exposure to sunlight for vitamin D synthesis, captive primates are supplemented with vitamin D (cholecalciferol). Vitamin D metabolite data from wild primates living indigenously could suggest optimum levels. The purpose of this study was to: 1) to explore whether baboons, a speciose genus whose members have significant exposed skin, coat color variation and wide geographical distribution, mirrors the skin pigmentation-vitamin D relationship found in humans; 2) compare vitamin D metabolite levels in wild and captive members of the same or similar baboon species; and 3) apply a recently developed method currently used in humans for measuring multiple vitamin D metabolites as a panel to explore if/how these metabolites can inform us on vitamin D sufficiency. Serum samples from males of three baboon species in the wild: Papio anubis (olive baboon, dark exposed skin), P. cynocephalus (yellow baboon, brown exposed skin), and P. hamadryas (hamadryas baboon, pink exposed skin), were compared with vitamin D supplemented captive olive baboons with sun exposure. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) measured vitamin D and its main metabolites. Cholecalciferol, 25 hydroxyvitamin D (25(OH)D ), and 24,25 dihydroxyvitamin D (24,25(OH) D ), showed significant differences by species. The levels of cholecalciferol due to supplements in the captive olive baboons did not convert to higher 25(OH)D while the wild olive baboons exhibited the lowest levels for both cholecalciferol and 25(OH)D . Further metabolic conversion of 25(OH)D to 24,25(OH) D indicated that all baboons had more similar conversion ratios and these were within the same range found for humans that are depicted as having adequate vitamin D levels. This study provided evidence that exposed skin color does influence vitamin D3 levels, with lower levels in darker skinned species, but these differences are eliminated in the downstream metabolite conversion indicating strong regulatory control.
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http://dx.doi.org/10.1002/ajp.22935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390488PMC
December 2018