Publications by authors named "Bart L Clarke"

89 Publications

Normocalcemic Primary Hyperparathyroidism: Need for a Standardized Clinical Approach.

Endocrinol Metab (Seoul) 2021 Jun 1;36(3):525-535. Epub 2021 Jun 1.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.

Since normocalcemic primary hyperparathyroidism (NHPT) was first defined at the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008, many papers have been published describing its prevalence and possible complications. Guidelines for the management of this condition are still lacking, and making the diagnosis requires fulfillment of strict criteria. Recent studies have shown that intermittent oscillations of serum calcium just below and slightly above the normal limits are very frequent, therefore challenging the assumption that serum calcium must be consistently normal to make the diagnosis. There is debate if these variations in serum calcium outside the normal range should be included under the rubric of NHPT or, rather, a milder form of classical primary hyperparathyroidism. Innovative approaches to define NHPT have been proposed that still need to be validated in prospective studies. Non-classical complications, especially cardiovascular complications, have been associated with NHPT, indicating that hyperparathyroidism may be a cardiovascular risk factor. New associations between parathyroid hormone (PTH) and several other comorbidities have also been reported from observational studies, suggesting that excessive PTH secretion might cause tissue dysfunction independent of serum calcium. Heterogeneous studies using different definitions of NHPT, however, make it difficult to draw definitive conclusions regarding the role of PTH excess when complications other than osteoporosis or kidney stones are described. This review will focus on clinical aspects and suggest an approach to NHPT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3803/EnM.2021.1061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258342PMC
June 2021

Glucocorticoid- and Transplantation-Induced Osteoporosis.

Endocrinol Metab Clin North Am 2021 Jun;50(2):251-273

Mayo Clinic E18-A, 200 1st Street Southwest, Rochester, MN 55905, USA. Electronic address:

Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis; nonetheless, it remains an undertreated condition. Transplantation-induced osteoporosis encompasses a broad range of unique pathogenetic features with distinct characteristics dependent on the transplanted organ. Understanding the pathogenesis of bone loss is key to recommending osteoporosis therapy in these patients. This review summarizes recent advances and addresses current issues in these fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecl.2021.03.002DOI Listing
June 2021

Basal Ganglia Calcification Is Associated With Local and Systemic Metabolic Mechanisms in Adult Hypoparathyroidism.

J Clin Endocrinol Metab 2021 Jun;106(7):1900-1917

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.

Context: Hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone, which may be associated with soft tissue calcification in the basal ganglia of the brain.

Objective: To assess the prevalence and factors involved in the pathophysiology of basal ganglia calcification (BGC) in the brain in chronic hypoparathyroidism and to evaluate proposed pathophysiologic mechanisms.

Design: Case-control study with retrospective review of medical records over 20 years.

Setting: Single academic medical center.

Patients: 142 patients with chronic hypoparathyroidism and computed tomography (CT) head scans followed between January 1, 2000 and July 9, 2020, and 426 age- and sex-matched controls with CT head scans over the same interval.

Interventions: None.

Main Outcome Measures: Demographic, biochemical, and CT head imaging findings, with semiquantitative assessment of volumetric BGC.

Results: The study found that 25.4% of 142 patients followed for a median of 17 years after diagnosis of chronic hypoparathyroidism had BGC, which developed at a younger age than in controls. BGC was 5.1-fold more common in nonsurgical patients and less common in postsurgical patients. Low serum calcium and low calcium/phosphate ratio correlated with BGC. Neither serum phosphorus nor calcium × phosphate product predicted BGC. Lower serum calcium was associated with greater volume of BGC. The extent of BGC varied widely, with nonsurgical patients generally having a greater volume and distribution of calcification.

Conclusions: BGC is associated with low serum calcium and low serum calcium/phosphate ratio, which may be related to severity of the disease, its etiology, or duration of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab162DOI Listing
June 2021

Challenges in the management of chronic hypoparathyroidism.

Endocr Connect 2020 Sep 1. Epub 2020 Sep 1.

B Clarke, Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, United States.

The first adjunctive hormone therapy for chronic hypoparathyroidism, recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] was approved by the FDA in January 2015. Since the approval of rhPTH(1-84), growing interest has developed in other agents to treat this disorder in both the scientific community and among pharmaceutical companies. For several reasons, conventional therapy with calcium and activated vitamin D supplementation, magnesium supplementation as needed, and occasionally thiazide-type diuretic therapy remains the mainstay of treatment, while endocrinologists and patients are constantly challenged by limitations of conventional treatment. Serum calcium fluctuations, increased urinary calcium, hyperphosphatemia, and a constellation of symptoms that limit mental and physical functioning are frequently associated with conventional therapy. Understanding how conventional treatment and hormone therapy work in terms of pharmacokinetics and pharmacodynamics is key to effectively managing chronic hypoparathyroidism. Multiple questions remain regarding the effectiveness of PTH adjunctive therapy in preventing or slowing the onset and progression of the classical complications of hypoparathyroidism, such as chronic kidney disease, calcium-containing kidney stones, cataracts, or basal ganglia calcification. Several studies point toward an improvement in quality of life during replacement therapy. This review will discuss current clinical and research challenges posed by treatment of chronic hypoparathyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-20-0366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707836PMC
September 2020

Ethical Challenges in COVID-19 Biospecimen Research: Perspectives From Institutional Review Board Members and Bioethicists.

Mayo Clin Proc 2021 01 23;96(1):165-173. Epub 2020 Oct 23.

Office for Human Research Protection and Institutional Review Board, Mayo Clinic, Rochester, MN; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.

Biospecimen research is a prominent investigative strategy that aims to provide novel insights into coronavirus disease 2019 (COVID-19), inform clinical trials, and develop effective, life-saving treatments. However, COVID-19 biospecimen research raises accompanying ethical concerns and practical challenges for investigators and participants. In this special article, we discuss the ethical issues that are associated with autonomy, beneficence, and justice in COVID-19 biospecimen research and describe strategies to manage the practical challenges, with an emphasis on protecting the rights and welfare of human research participants during a pandemic response. Appropriate institutional review board oversight and bioethics guidance for COVID-19 biospecimen research must maintain their focus on protecting the rights and welfare of research participants, despite the urgent need for more knowledge about the virus and the threat it poses to communities and nations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2020.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584427PMC
January 2021

Premenopausal osteoporosis: Focus on the female athlete triad.

Case Rep Womens Health 2021 Jan 27;29:e00276. Epub 2020 Nov 27.

Mayo Clinic, Minnesota, Rochester, MN, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.crwh.2020.e00276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736898PMC
January 2021

Reply to Corticosteroid-Induced Osteonecrosis in COVID-19: A Call for Caution.

J Bone Miner Res 2020 10 18;35(10):2084-2085. Epub 2020 Aug 18.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461272PMC
October 2020

Normocalcemic Hyperparathyroidism: A Heterogeneous Disorder Often Misdiagnosed?

JBMR Plus 2020 Aug 24;4(8):e10391. Epub 2020 Jul 24.

Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic Rochester Minnesota USA.

Normocalcemic primary hyperparathyroidism (NHPT) was first described over 10 years ago, but uncertainties still remain about its definition, prevalence, and rates of complications. As a result, consensus management guidelines for this condition have not yet been published. Several hypotheses have been proposed for the pathophysiology of NHPT, but it may be a heterogeneous disorder with multiple causes, rather than a single etiology that explains this biochemical phenotype. A common clinical concern is whether NHPT should be treated surgically when complications are already present at first recognition of the disorder, rather than following patients clinically over time. The literature on NHPT is based mostly on larger studies of population-based cohorts and smaller studies from referral centers. Lack of rigorous diagnostic criteria and selection bias inherent in populations seen at tertiary referral centers may explain the heterogeneity of reported rates of bone and renal complications in relation to consistently mild laboratory alterations. Unresolved questions remain about the significance of NHPT when it is diagnosed biochemically without evident bone or kidney complications. Moreover, its natural history remains to be elucidated because a proportion of what is classified as NHPT may revert to normal spontaneously, thus revealing previously unrecognized secondary hyperparathyroidism. These issues indicate that caution should be used in recommending surgery for NHPT. This review will focus on recent issues regarding the pathophysiology, evaluation, and management of NHPT. © 2020 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm4.10391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422713PMC
August 2020

A bridge too far? Attempting to bridge the treatment gap in osteoporosis.

Endocrine 2020 08 21;69(2):241-243. Epub 2020 May 21.

San Francisco, Endocrine Research Unit-111N, San Francisco Department of Veterans Affairs Medical Center, University of California, 1700 Owens Street, 3rd Floor, Room 369, San Francisco, CA, 94158, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-020-02346-wDOI Listing
August 2020

Osteoporosis Management in the Era of COVID-19.

J Bone Miner Res 2020 06 26;35(6):1009-1013. Epub 2020 May 26.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.

Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available. © 2020 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273005PMC
June 2020

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

J Orthop Trauma 2020 Apr;34(4):e125-e141

Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BOT.0000000000001743DOI Listing
April 2020

Bone metastases in thyroid cancer.

J Bone Oncol 2020 Apr 19;21:100282. Epub 2020 Feb 19.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, 200 First Street SW Rochester, MN, 55905, USA.

Whereas preemptive screening for the presence of lymph node and lung metastases is standard-of-care in thyroid cancer patients, bone metastases are less well studied and are often neglected in thyroid cancer patient surveillance. Bone metastases in thyroid cancer are, however, independently associated with poor/worse prognosis with a median overall survival from detection of only 4 years despite an otherwise excellent prognosis for the vast majority of thyroid cancer patients. In this review we summarize the state of current knowledge as pertinent to bony metastatic disease in thyroid cancer, including clinical implications, impacts on patient function and quality of life, pathogenesis, and therapeutic opportunities, proposing approaches to patient care accordingly. In particular, bone metastasis pathogenesis appears to reflect cooperatively between cancer and the bone microenvironment creating a "vicious cycle" of bone destruction rather than due exclusively to tumor invasion into bone. Additionally, bone metastases are more frequent in follicular and medullary thyroid cancers, requiring closer bone surveillance in patients with these histologies. Emerging data also suggest that treatments such as multikinase inhibitors (MKIs) can be less effective in controlling bone, as opposed to other (e.g. lung), metastases in thyroid cancers, making special attention to bone critical even in the setting of active MKI therapy. Although locoregional therapies including surgery, radiotherapy and ablation play important roles in palliation, antiresorptive agents including bisphosphonates and denosumab appear individually to delay and/or lessen skeletal morbidity and complications, with dosing frequency of every 3 months appearing optimal; their early application should therefore be strongly considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbo.2020.100282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058902PMC
April 2020

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism.

Nat Commun 2020 01 7;11(1):87. Epub 2020 Jan 7.

Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-14003-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946812PMC
January 2020

Burden of illness in not adequately controlled chronic hypoparathyroidism: Findings from a 13-country patient and caregiver survey.

Clin Endocrinol (Oxf) 2020 02 11;92(2):159-168. Epub 2019 Dec 11.

Section of Specialized Endocrinology, Oslo University Hospital, Oslo, Norway.

Objective: To address knowledge gaps regarding burdens associated with not adequately controlled chronic hypoparathyroidism.

Design: Global patient and caregiver survey.

Study Populations: Patients with chronic hypoparathyroidism not adequately controlled on conventional therapy and their caregivers.

Measurements: Health-related quality of life (HRQoL) and health status were evaluated using the 36-item Short Form version 2 (SF-36 v2.0) and Five-Level EuroQoL 5 Dimensions (EQ-5D-5L) instruments, respectively. Hypoparathyroidism-associated symptoms were assessed by a disease-specific Hypoparathyroidism Symptom Diary and caregiver burden via the Modified Caregiver Strain Index (MCSI).

Results: Data were obtained from 398 patients and 207 caregivers. Patients' self-rated hypoparathyroidism-related symptom severity was none (3%), mild (32%), moderate (53%) or severe (12%). Per the Hypoparathyroidism Symptom Diary, patients reported moderate, severe or very severe symptoms of physical fatigue (73%), muscle cramps (55%), heaviness in limbs (55%) and tingling (51%) over a 7-day recall period. Impacts (rated 'somewhat' or 'very much') were reported by 84% of patients for ability to exercise, 78% for sleep, 75% for ability to work and 63% for family relationships. Inverse relationships were observed between patient self-rated overall symptom severity and HRQoL and health status assessment scores-the greater the symptom severity, the lower the SF-36 and EQ-5D-5L scores. Caregiver burden increased with patient self-rated symptom severity: none, 1.7 MCSI; mild, 5.4 MCSI; moderate, 9.5 MCSI; and severe, 12.5 MCSI.

Conclusion: Patients with not adequately controlled hypoparathyroidism reported substantial symptoms and impacts. Greater patient symptom severity was associated with decreased patient HRQoL and health status assessments and increased caregiver burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cen.14128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027891PMC
February 2020

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

J Bone Miner Res 2020 01 1;35(1):36-52. Epub 2019 Dec 1.

Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). © 2019 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3877DOI Listing
January 2020

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism.

J Clin Endocrinol Metab 2019 11;104(11):5136-5147

Section of Endocrinology, University of Chicago Medicine, Chicago, Illinois.

Context: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency.

Objective: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)].

Design: Open-label extension study; 5-year interim analysis.

Setting: 12 US centers.

Patients: Adults (N = 49) with chronic hypoparathyroidism.

Intervention(s): rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum.

Main Outcome Measure(s): Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal.

Results: Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline.

Conclusion: Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2019-01010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760337PMC
November 2019

Transgender bone health.

Maturitas 2019 Sep 14;127:35-42. Epub 2019 May 14.

Mayo Clinic E18-A, 200 1st Street SW, Rochester, MN, 55905, United States. Electronic address:

Gonadal sex steroids play a pivotal role in bone health. Medical and surgical therapies for gender dysphoria in both adolescents and adults can lead to skeletal changes. This review evaluates the literature on transgender bone health, and how the data can be translated into clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.maturitas.2019.05.002DOI Listing
September 2019

A Lot of Progress, With More to Be Done: A Response to NIH Pathways to Prevention Report "Research Gaps for Long-Term Drug Therapies for Osteoporotic Fracture Prevention".

J Bone Miner Res 2019 09 25;34(9):1549-1551. Epub 2019 Jul 25.

Harvard Medical School, Musculoskeletal Research Center, Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

The public health implications of osteoporosis are enormous but the disease remains underdiagnosed and undertreated. In October 2018, the National Institutes of Health (NIH) convened a Pathways to Prevention (P2P) Workshop entitled "Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention" designed to identify research gaps, suggest future research opportunities, and advance the field through an evidence-based assessment. By design, the P2P report focused on "gaps" in our knowledge base. Unfortunately, however, the report did not sufficiently acknowledge the current evidence that unequivocally demonstrates the therapeutic efficacy of existing pharmacologic therapies for osteoporosis, which has the potential to exacerbate the current crises in osteoporosis diagnosis and treatment. © 2019 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082897PMC
September 2019

Institutional Review Boards: What Clinician Researchers Need to Know.

Mayo Clin Proc 2019 03;94(3):515-525

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN; Mayo Clinic Institutional Review Board, Mayo Clinic, Rochester, MN.

The institutional review board (IRB) is a group federally mandated to review and monitor research involving humans to ensure protection of their rights and welfare as research participants. Clinicians engaged in research require IRB approval for all research involving human participants, whether living individuals, data, or specimens. The process for obtaining IRB approval may seem like a daunting task. However, it is critical for clinical researchers to conduct research in a manner that protects human participants, and it is the mission of the IRB to help researchers accomplish this task. The purpose of this article is to review the role and purpose of the IRB, highlight federal and regulatory standards in human research participants protection, and help clinical researchers have a broader understanding of IRB functions that will help them conduct high-quality research with human participants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2019.01.020DOI Listing
March 2019

Is It Time to Stop (or Pause) Vertebral Augmentation?

J Bone Miner Res 2019 01;34(1):1-2

Mayo Clinic College of Medicine, Rochester, MN, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122647PMC
January 2019

Asymptomatic Primary Hyperparathyroidism.

Authors:
Bart L Clarke

Front Horm Res 2019 19;51:13-22. Epub 2018 Nov 19.

Asymptomatic primary hyperparathyroidism has become the most common presentation of primary hyperparathyroidism in Europe and North America, and an increasingly common presentation in other parts of the world. As many as 25% of asymptomatic patients may develop indications for parathyroidectomy when followed long-term for up to 15 years. Patients who remain asymptomatic should be monitored for the development of complications that justify surgery. Patients who become symptomatic should be referred for surgery. Surgery may improve quality of life even in patients who remain asymptomatic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000491035DOI Listing
April 2019

Epidemiology and Complications of Hypoparathyroidism.

Authors:
Bart L Clarke

Endocrinol Metab Clin North Am 2018 12 11;47(4):771-782. Epub 2018 Oct 11.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, E18-A, 200 1st Street SW, Rochester, MN 55905, USA. Electronic address:

Until recently, very few studies have described the epidemiology of this rare disorder. Several large population-based studies have recently been published describing the prevalence and incidence of hypoparathyroidism in various countries. Some of these studies have described the epidemiology of both postsurgical and nonsurgical hypoparathyroidism. In addition, a number of studies have now been published describing the prevalence of complications of this disorder. This article summarizes the published medical literature regarding the prevalence and incidence of this disorder, and the risk of known complications of hypoparathyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecl.2018.07.004DOI Listing
December 2018

Causes of low peak bone mass in women.

Maturitas 2018 May 15;111:61-68. Epub 2017 Dec 15.

Mayo Clinic E18-A, 200 1st Street SW, Rochester, MN, 55905, USA. Electronic address:

Peak bone mass is the maximum bone mass that accrues during growth and development. Consolidation of peak bone mass normally occurs during early adulthood. Low peak bone mass results from failure to achieve peak bone mass genetic potential, primarily due to bone loss caused by a variety of conditions or processes occurring at younger ages than usual. Recognized causes of low peak bone mass include genetic causes, endocrine disorders, nutritional disorders, chronic diseases of childhood or adolescence, medications, and idiopathic factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.maturitas.2017.12.010DOI Listing
May 2018

Recombinant Human Parathyroid Hormone Effect on Health-Related Quality of Life in Adults With Chronic Hypoparathyroidism.

J Clin Endocrinol Metab 2018 02;103(2):722-731

Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, New York.

Context: Reduced health-related quality of life (HRQoL) is common in patients with hypoparathyroidism treated conventionally with calcium and active vitamin D supplements.

Objective: To examine the effects of recombinant human parathyroid hormone [rhPTH(1-84)] on HRQoL as measured by the 36-Item Short-Form Health Survey (SF-36) during a multinational, randomized, placebo-controlled study.

Patients: Adults (N = 122) with chronic hypoparathyroidism.

Intervention(s): After an optimization period when calcium and/or active vitamin D supplements were adjusted to reach target serum calcium levels (8.0 to 9.0 mg/dL; 2.0 to 2.2 mmol/L), patients were randomly assigned to receive placebo (n = 39) or rhPTH(1-84) (n = 83) (starting dose, 50 μg/d, could be titrated up to 100 μg/d); supplement doses were adjusted to maintain target serum calcium levels.

Main Outcome Measure(s): Change from baseline (postoptimization, at randomization) to week 24 in HRQoL as assessed by the SF-36.

Results: Overall, the between-group differences were not statistically significant. However, in the rhPTH(1-84) group, there were significant improvements in the physical component summary score (P = 0.004), and in body pain (P < 0.05), general health (P < 0.05), and vitality (P < 0.001) domains as compared with baseline values. In the placebo group, there were no significant changes for any domains. The magnitude of change between 0 and 24 weeks in SF-36 scores was negatively correlated with baseline scores, such that patients with lower HRQoL at baseline were more likely to experience improvement in response to treatment.

Conclusion: Treatment with rhPTH(1-84) may improve HRQoL in adults with hypoparathyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2017-01471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458961PMC
February 2018

Hypoparathyroidism.

Nat Rev Dis Primers 2017 Oct 5;3:17080. Epub 2017 Oct 5.

This corrects the article DOI: 10.1038/nrdp.2017.55.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nrdp.2017.80DOI Listing
October 2017

Safety and Efficacy of Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism Randomly Assigned to Receive Fixed 25-μg or 50-μg Daily Doses.

Clin Ther 2017 Oct 21;39(10):2096-2102. Epub 2017 Sep 21.

Shire Human Genetic Therapies Inc, Lexington, Massachusetts.

Purpose: The present study examined the efficacy and safety of a lower rhPTH(1-84) dose.

Methods: RELAY was a dose-blinded, multicenter, 8-week study of patients with hypoparathyroidism randomized to fixed 25- or 50-μg/d doses of subcutaneous rhPTH(1-84). The primary end point was the percentage of patients at week 8 with supplement reductions in calcium to ≤500 mg/d and in calcitriol to ≤0.25 μg/d, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. The secondary end point was the percentage of patients at week 8 with a ≥50% reduction in calcium and calcitriol doses, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal.

Findings: Forty-two patients were randomized (25-μg group, n = 19; 50-μg group, n = 23). At week 8, the primary end point was achieved by 4 (21%; 95% CI, 6%-46%) and 6 (26%; 95% CI, 10%-48%) of the patients receiving 25 and 50 μg/d of rhPTH(1-84), respectively. The secondary end point was achieved by 2 (11%; 95% CI, 1%-33%) and 6 (26%; 95% CI, 10%-48%) of the patients receiving 25 and 50 μg/d of rhPTH(1-84), respectively. Treatment-emergent adverse events were reported by 11 (58%) patients in the 25-μg group and 17 (74%) patients in the 50-μg group.

Implications: Doses as low as 25 µg/d of rhPTH(1-84) are well tolerated and may be effective for a subset of patients. ClinicalTrials.gov identifier: NCT01268098.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2017.08.011DOI Listing
October 2017

Hypoparathyroidism.

Nat Rev Dis Primers 2017 08 31;3:17055. Epub 2017 Aug 31.

Endocrine Research Unit, San Francisco Department of Veterans Affairs Medical Center, University of California, San Francisco, California, USA.

Hypoparathyroidism is a disease characterized by inadequately low circulating concentrations of parathyroid hormone (PTH) resulting in low calcium levels and increased phosphate levels in the blood. Symptoms of the disease result from increased neuromuscular irritability caused by hypocalcaemia and include tingling, muscle cramps and seizures. The most common cause of the disease is inadvertent removal of, or injury to, the parathyroid glands during neck surgery, followed by genetic, idiopathic and autoimmune aetiologies. Conventional treatment includes activated vitamin D and/or calcium supplements, but this treatment does not fully replace the functions of PTH and can lead to short-term problems (such as hypocalcaemia, hypercalcaemia and increased urinary calcium excretion) and long-term complications (which include nephrocalcinosis, kidney stones and brain calcifications). PTH replacement has emerged as a new treatment option. Clinical trials using human PTH(1-34) and PTH(1-84) showed that this treatment was safe and effective in studies lasting up to 6 years. Recombinant human PTH(1-84) has been approved in the United States and Europe for the management of hypoparathyroidism; however, its effect on long-term complications is still being evaluated. Clinical practice guidelines, which describe the consensus of experts in the field, have been published and recognize the need for more research to optimize care. In this Primer, we summarize current knowledge of the prevalence, pathophysiology, clinical presentation and management of hypoparathyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nrdp.2017.55DOI Listing
August 2017

Biochemical Testing Relevant to Bone.

Endocrinol Metab Clin North Am 2017 09 20;46(3):649-667. Epub 2017 Jun 20.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, E-18A, 200 1st Street Southwest, Rochester, MN 55905, USA. Electronic address:

Laboratory biochemical testing is critical to the clinical understanding of bone disorders. Patients with skeletal diseases have underlying themes in their pathophysiology that would be impossible to detect without biochemical assessment of serum and urine minerals, vitamin D, parathyroid hormone, parathyroid hormone-related peptide, and bone turnover markers. Bone disorders are caused by abnormalities in signaling pathways that affect bone formation and resorption. Therapies for common bone diseases were developed in direct response to underlying biochemical abnormalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecl.2017.04.003DOI Listing
September 2017

Melorheostosis: a Rare Sclerosing Bone Dysplasia.

Curr Osteoporos Rep 2017 08;15(4):335-342

Mayo Clinic, E18-A, 200 1st Street SW, Rochester, MN, 55905, USA.

Purpose Of Review: Melorheostosis is a rare sclerosing bone dysplasia that affects both cortical bone and adjacent soft tissue structures in a sclerotomal distribution. In this review, we describe the natural history, radiological features, proposed pathogenesis, and management options for this debilitating condition.

Recent Findings: Since its first description in 1922, about 400 cases of melorheostosis have been reported, either as single reports or in small case series. Melorheostosis affects the appendicular skeleton more commonly than the axial skeleton and usually presents with lower limb deformity. Diagnosis is based on a combination of clinical and radiological features that help differentiate this condition from other sclerosing bone dysplasias. LEM domain-containing protein 3 (LEMD3) gene mutations have been demonstrated in several familial cases, but these have been more strongly correlated with other hereditary dysplasias, such as osteopoikilosis, and are not thought to be the causative gene for melorheostosis. The exact etiology of classic sporadically occurring melorheostosis remains unknown, with possible causes being somatic LEMD3 mutations, somatic mutations in the bone morphogenetic protein/transforming growth factor-beta pathway, mutations in multiple genes, or other non-genetic causes. Management in recent years has involved nitrogen-containing bisphosphonates in addition to traditional orthopedic surgical approaches and physical therapy. Melorheostosis may present as mixed or atypical osseous involvement in addition to the classically described "dripping candle wax" appearance of hyperostosis. Some patients may have overlap with osteopoikilosis or Buschke-Ollendorff syndrome. In the future, better characterization of genetic and developmental factors predisposing to melorheostosis may lead to the development of targeted therapy for this condition, as well as for more commonly encountered skeletal abnormalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11914-017-0375-yDOI Listing
August 2017