Mol Diagn Ther 2017 Mar 7. Epub 2017 Mar 7.

Department of Internal Medicine Specialties, Division of Bone Diseases, University Hospital of Geneva, 64 Av de la Roseraie, CH-1205, Geneva, Switzerland.

The measurement of bone turnover markers is useful for the clinical investigation of patients with osteoporosis. Among the available biochemical markers, the measurements of serum procollagen type I N-terminal propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) have been recommended as reference markers of bone formation and bone resorption, respectively. The important sources of preanalytical and analytical variability have been identified for both markers, and precise measurement can now be obtained. Read More

J Hand Surg Am 2017 Feb;42(2):71-77

Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Boston, MA. Electronic address:

Purpose: To examine whether premenopausal women with distal radius fractures (DRF) have lower levels of 25-hydroxyvitamin D (25[OH]D) and increased levels of serum bone turnover markers (BTM) compared with control subjects without fracture.

Methods: Premenopausal women with DRF (n = 20) were prospectively enrolled and compared with age-matched individuals without a fracture (n = 20). Outcome measures included serum levels of 25(OH)D, parathyroid hormone (PTH), markers of bone formation (osteocalcin [OC], N-terminal extension propeptide of type I collagen [P1NP], and bone-specific alkaline phosphatase [BSAP]), and markers of bone resorption (C-terminal telopeptide of type I collagen [CTX]). Read More

Clin Chem 2017 Feb 9;63(2):464-474. Epub 2016 Dec 9.

Endocrine Unit, Massachusetts General Hospital, Boston, MA.

Background: Disorders of bone metabolism, most notably osteoporosis, are highly prevalent and predispose to fractures, causing high patient morbidity and mortality. Diagnosis and monitoring of bone metabolic defects can present a major challenge as these disorders are largely asymptomatic and radiographic measures of bone mass respond slowly to changes in bone physiology.

Content: Bone turnover markers (BTMs) are a series of protein or protein derivative biomarkers released during bone remodeling by osteoblasts or osteoclasts. Read More

Mol Ther Nucleic Acids 2016 Sep 13;5(9):e363. Epub 2016 Sep 13.

NanoMedicines Research Group, Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.

Sclerostin is a protein secreted by osteocytes that is encoded by the SOST gene; it decreases bone formation by reducing osteoblast differentiation through inhibition of the Wnt signaling pathway. Silencing the SOST gene using RNA interference (RNAi) could therefore be an effective way to treat osteoporosis. Here, we investigate the utility of lipid nanoparticle (LNP) formulations of siRNA to silence the SOST gene in vitro and in vivo. Read More

Endocrine 2016 May 23;52(2):222-5. Epub 2016 Feb 23.

Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, 102-118 Murdoch Drive, Murdoch, WA, 6150, Australia.

The purpose of the present study was to examine of the current role of bone turnover markers (BTMs) in the management of osteoporosis. Perusal of the literature examines the available evidence for the utility of BTMs for decision to treat and for the monitoring of treatment for osteoporosis. There is no evidence for the use of BTMs for fracture risk calculation, decision to treat or for treatment selection. Read More

J Bone Miner Res 2016 Apr 24;31(4):874-81. Epub 2016 Jan 24.

Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.

Mutations in the LRP4 gene, coding for a Wnt signaling coreceptor, have been found to cause several allelic conditions. Among these, two are characterized by a strong skeletal involvement, namely sclerosteosis and Cenani-Lenz syndrome. In this work, we evaluated the role of LRP4 in the pathophysiology of these diseases. Read More

Clin Calcium 2015 Jan;25(1):105-13

Department of Obstetrics and Gynecology, Hori Hospital, Japan.

The target to treat osteoporosis is prevention for future fractures. After the evaluation of cathepsin K inhibitors (CKIs) which was developed as antresorptive agents, there is evidence that these agents also possess anabolic activity, suggesting that CKIs differ from so called antiresorptive agents such as bisphosphonates and denosumab. The classification of agents for treatment of osteoporosis has been changed. Read More

J Clin Endocrinol Metab 2015 Jan;100(1):90-9

School of Pathology and Laboratory Medicine (S.A.P.C., J.P.B., S.D.V.) and School of Medicine and Pharmacology (S.A.P.C., L.M., L.F., B.B.Y.), University of Western Australia, Crawley, Western Australia 6009, Australia; Biochemistry Department (S.A.P.C., E.B., J.P.B., S.D.V.), PathWest Laboratory Medicine, Nedlands, 6009 Western Australia, Australia; Department of Medicine (P.R.E.), Monash University, Clayton, Victoria 3146, Australia; Queensland Research Centre for Peripheral Vascular Disease (J.G.), School of Medicine and Dentistry, James Cook University, Townsville 4811, Queensland; Department of Vascular and Endovascular Surgery (J.G.), The Townsville Hospital, Townsville, Queensland 4810, Australia; and Department of Endocrinology and Diabetes (B.B.Y.), Fremantle Hospital, Fremantle 6160, Western Australia, Australia.

Context: Reference intervals for bone turnover markers (BTMs) and relationships between BTM and fracture risk in older men are not well characterized.

Objective: The purpose of this article was to determine the reference intervals for serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (PINP), and collagen type I C-terminal cross-linked telopeptide (CTX-I) in healthy older men and to explore factors associated with BTMs, including hip fracture risk.

Participants And Setting: We studied a population-based cohort of 4248 men aged 70 to 89 years, 4008 of whom had serum samples available for analysis. Read More

Osteoporos Int 2015 Feb 16;26(2):617-27. Epub 2014 Sep 16.

Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium,

Summary: The aim of this study was to determine whether bone turnover markers (BTMs) predict changes in areal bone mineral density (aBMD) in middle-aged and elderly European men. Older men with high bone turnover are at a higher risk of accelerated hip bone loss, but the clinical utility of BTMs in individuals is limited.

Introduction: Prospective studies on the value of BTMs to predict changes in aBMD in men are few and conflicting. Read More

Clin J Am Soc Nephrol 2014 Jul 19;9(7):1160-2. Epub 2014 Jun 19.

Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, New York

Maturitas 2014 Jul 2;78(3):199-204. Epub 2014 May 2.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:

Monoclonal antibodies to molecular targets important for bone formation and bone resorption are being investigated for treatment of postmenopausal osteoporosis. Postmenopausal osteoporosis is characterized by increased bone turnover, with bone resorption typically exceeding bone formation. These pathophysiological changes cause decreased bone mineral density and disruption of bone microarchitecture which lead to low-trauma fractures. Read More

Health Technol Assess 2014 Feb;18(11):1-180

Centre for Reviews and Dissemination, York, UK.

Background: There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. Read More

Haemophilia 2014 Mar 7;20(2):268-75. Epub 2013 Oct 7.

Haemophilia Centre of Northern Greece, Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) remains unknown. The aim of this study was to evaluate bone metabolism in men with haemophilia and to investigate associations between BTM and bone disease. Read More

J Transl Med 2013 Aug 29;11:201. Epub 2013 Aug 29.

Department of Biochemistry, The James Cook University Hospital, Middlesbrough TS4 3BW, UK.

Osteoporosis is characterised by low bone mass and structural deterioration of bone tissue, resulting in increased fragility and susceptibility to fracture. Osteoporotic fractures are a significant cause of morbidity and mortality. Direct medical costs from such fractures in the UK are currently estimated at over two billion pounds per year, resulting in a substantial healthcare burden that is expected to rise exponentially due to increasing life expectancy. Read More

Org Biomol Chem 2013 Sep;11(35):5747-71

Department of Biomedical Sciences for Health, University of Milan, via F.lli Cervi 93, 20090 Segrate (Milan), Italy.

This review focuses on the chemical structure, biosynthesis and synthesis of free and glycosylated pyridinolines (Pyds), fluorescent collagen cross-links, with a pyridinium salt structure. Pyds derive from the degradation of bone collagen and have attracted attention for their use as biochemical markers of bone resorption and to assess fracture risk prediction in persons suffering from osteoporosis, bone cancer and other bone or collagen diseases. We consider and critically discuss all reported syntheses of free and glycosylated Pyds evidencing an unrevised chemistry, original and of general utility, analysis of which allows us to also support a previously suggested non-enzymatic formation of Pyds in collagen better rationalizing and justifying the chemical events. Read More

Ir J Med Sci 2014 Mar 5;183(1):47-52. Epub 2013 Jun 5.

Metabolism Laboratory, St. Vincent's University Hospital, Dublin, Ireland,

Background: Tartrate-resistant acid phosphatase isoform 5b (TRACP5b) is a serum bone resorption marker. Our aim was to investigate its utility in monitoring metabolic bone disease.

Methods: Serum TRACP5b, C-terminal cross-linking telopeptide of type I collagen, urine N-terminal cross-linking telopeptide of type I collagen and free deoxypyridinoline were measured pre- and post-treatment with a parathyroid hormone analogue [PTH (1-34)] (n = 14) or a bisphosphonate (N-BP) (n = 8). Read More

Clin Lab 2012 ;58(7-8):845-50

Department of Orthopaedics, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.

Background: The goal was to find out the clinical significances of tartrate-resistant acid phosphatase isoform 5b (TRACP 5b), a biomarker of bone resorption, and bone alkaline phosphatase (BAP) and osteocalcin, two markers of bone formation, in evaluating the osteoporotic fracture risk in Chinese patients.

Methods: Thirty six Chinese osteoporotic fracture patients and 32 Chinese healthy subjects were included in the study. Bone mineral density (BMD) of lumbar spine and total body were determined by dual-energy X-ray absorptiometry in all subjects. Read More

Osteoporos Int 2012 Oct 14;23(10):2425-33. Epub 2012 Jul 14.

University of California, San Francisco, USA.

Unlabelled: This position paper reviews how the National Bone Health Alliance (NBHA) will execute a project to help assure health professionals of the clinical utility of bone turnover markers; the current clinical approaches concerning osteoporosis and the status and use of bone turnover markers in the USA; the rationale for focusing this effort around two specific bone turnover markers; the need to standardize bone marker sample collection procedures, reference ranges, and bone turnover marker assays in clinical laboratories; and the importance of harmonization for future research of bone turnover markers.

Introduction: Osteoporosis is a major global health problem, with the prevalence and incidence of osteoporosis for at-risk populations estimated to be 44 million Americans. The potential of bone markers as an additional tool for health care professionals to improve patient outcomes and impact morbidity and mortality is crucial in providing better health care and addressing rising health care costs. Read More

Calcif Tissue Int 2012 Sep 11;91(3):204-14. Epub 2012 Jul 11.

Cranfield Health, Cranfield University, Cranfield, UK.

Multivariate prediction algorithms such as FRAX® and QFractureScores provide an opportunity for new prognostic biomarkers to be developed and incorporated, potentially leading to better fracture prediction. As more research is conducted into these novel biomarkers, a number of factors need to be considered for their successful development for inclusion in these algorithms. In this review, we describe two well-known multivariate prediction algorithms for osteoporosis fracture risk applicable to the UK population, FRAX and QFractureScores, and comment on the current prognostic tools available for fracture risk; dual X-ray assessment, quantitative ultrasonography, and genomic/biochemical markers. Read More

Int J Womens Health 2012 12;4:167-74. Epub 2012 Apr 12.

Department of Orthopedics and Traumatology, University Hospital Queen Giovanna - ISUL.

Bisphosphonates are the most widely prescribed treatment for postmenopausal osteoporosis, secondary osteoporosis, and male osteoporosis. Notwithstanding their high effectiveness and favorable safety profile, the adherence to bisphosphonate treatment remains low. Different treatment strategies aim to improve the clinical effectiveness of bisphosphonate therapy. Read More

J Osteoporos 2011 15;2011:704015. Epub 2011 Dec 15.

INSERM UMR 1033, Université de Lyon, Hôpital Edouard Herriot, Pavillon F, Place d'Arsonval, 69437 Lyon, France.

In men aged less than 60, the association of serum and urinary levels of biochemical bone turnover markers (BTMs) and bone mineral density (BMD) is weak or not significant. After this age, higher BTM levels are correlated weakly, but significantly, with lower BMD and faster bone loss. Limited data from the cohort studies suggest that BTM measurement does not improve the prediction of fragility fractures in older men in comparison with age, BMD, history of falls and fragility fractures. Read More

CPT Pharmacometrics Syst Pharmacol 2012 Nov 14;1:e14. Epub 2012 Nov 14.

Pfizer, Pharmacometrics, Global Clinical Pharmacology, Cambridge, Massachusetts, USA.

A mathematical model component that extends an existing physiologically based multiscale systems pharmacology model (MSPM) of calcium and bone homeostasis was developed, enabling prediction of nonlinear changes in lumbar spine bone mineral density (LSBMD). Data for denosumab, a monoclonal antibody osteoporosis treatment, dosed at several levels and regimens, was used for fitting the BMD component. Bone marker and LSBMD data extracted from the literature described on/off-treatment effects of denosumab over 48 months [Miller, P. Read More

Womens Health (Lond) 2011 Nov;7(6):689-98

Department of Bone Biology & Biomarkers, Nordic Bioscience A/S, Herlev, Denmark.

Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the last 20 years, biochemical markers of bone turnover have been implemented to a larger degree, and especially within the field of drug development. Read More

Osteoporos Int 2012 Apr 8;23(4):1191-8. Epub 2011 Sep 8.

Department of Medicine, University of Toronto, Toronto, ON, Canada.

Fractures are common in patients with chronic kidney disease (CKD) and associated with substantially high morbidity and mortality. Bone mass measurements are commonly used to assess fracture risk in the general population, but the utility of these measurements in patients with CKD, and specifically among those on hemodialysis, is unclear. This review will outline the epidemiology and etiology of fractures in patients with CKD with a particular emphasis on men and women on hemodialysis. Read More

Clin Interv Aging 2011 24;6:119-24. Epub 2011 May 24.

Endocrinology and Metabolism, McGuire Veterans Affairs Medical Center, Richmond, VA, USA.

While most older patients with osteoporosis are treated with antiresorptive bisphosphonates such as alendronate, risedronate, ibandronate, and zoledronic acid, such drugs have side effects, remain in bone for extended periods, and lead to poor adherence to chronic treatment. Denosumab is a humanized monoclonal antibody and antiresorptive agent that works by decreasing the activity of the receptor activator of nuclear factor kappa B ligand. In major trials in postmenopausal women, denosumab increased bone mineral density by dual energy x-ray absorptiometry in the spine, hip, and distal third of the radius and decreased vertebral, nonvertebral, and hip fractures. Read More

Endocr Pract 2011 Nov-Dec;17(6):873-9

Department of Medicine, Division of Endocrinology and Metabolism, Loyola University Medical Center, Maywood, Illinois 60153, USA.

Objective: To (1) assess the rate of reduction in bone turnover with vitamin D and bisphosphonate therapies and (2) evaluate the clinical utility of bone-specific alkaline phosphatase (BSAP) in monitoring treatment response.

Methods: We retrospectively reviewed medical records of patients with newly diagnosed osteopenia and osteoporosis from 2002 to 2009 at Loyola University Medical Center. A cohort of postmenopausal women with hip or spine T-scores of less than -1, normal serum creatinine, and no prior vitamin D or bisphosphonate therapy was divided into vitamin D-deficient (n = 29) and vitamin D-sufficient (n = 13) groups. Read More

Semin Arthritis Rheum 2011 Oct 19;41(2):157-69. Epub 2011 Apr 19.

Paris Descartes University, Cochin Hospital, Department of Rheumatology B, Paris, France.

Objectives: Serum bone turnover markers (sBTM) are used in clinical practice for patients undergoing postmenopausal osteoporosis therapy. The aim of this study was to systematically analyze the literature on the ability of sBTM to monitor therapy, focusing on the following 5 objectives: (1) pretreatment values and treatment choice; (2) short-term changes and clinical response; (3) sBTM effect on persistence to therapy; (4) sBTM ability to predict fracture risk after withdrawal of therapy; and (5) the prediction of serious adverse effects.

Methods: A systematic search on Medline completed manually was performed until November 2010 and was limited to postmenopausal osteoporosis and marketed therapies. Read More

Ann N Y Acad Sci 2011 Feb 29;1218:80-7. Epub 2010 Sep 29.

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

Osteonecrosis of the jaw (ONJ) has been hypothesized to result in part from a relative "oversuppression" of normal physiologic bone remodeling at the jaw brought about by bisphosphonate therapy. Biochemical markers of bone turnover give readily measurable information on integrated systemic bone remodeling activity, as measured by blood and urine assays. The intra- and interassay variability of most currently available assays is less than 10%, although many biological factors can influence levels of bone turnover markers. Read More

Ginecol Obstet Mex 2010 Jun;78(6):322-8

Hospital Universitario Dr. José Eleuterio González, Monterrey, Nuevo León.

Background: Osteoporosis affects 1 in 3 postmenopausal women and is associated with significant morbidity and mortality. The utility of bisphosphonates is often affected by lack of attachment and acceptance of treatment.

Objective: To analyze the impact of biofeedback in the adherence to once-monthly oral ibandronate treatment. Read More

J Clin Densitom 2010 Apr-Jun;13(2):181-9. Epub 2010 Mar 27.

Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Bone turnover markers may provide a more rapid indication of patient response to osteoporosis treatment than bone mineral density (BMD) measurements. This post hoc analysis of data from the MOBILE (Monthly Oral iBandronate In LadiEs) study assessed the relationship between increases in BMD at 12 mo from baseline after starting ibandronate treatment and changes in bone resorption marker serum C-terminal telopeptide of type I collagen (sCTX) from baseline at 3 and 6 mo. MOBILE enrolled postmenopausal women aged 55-80 yr with mean lumbar spine (LS) BMD T-score of -2. Read More

Rev Endocr Metab Disord 2010 Dec;11(4):261-73

New Mexico Clinical Research & Osteoporosis Center, 300 Oak St. NE, Albuquerque, NM 87106, USA.

Osteoporosis is a common disease characterized by low bone strength that increases the risk of fractures. The consequences of fractures include increases in morbidity, mortality, and healthcare costs. Randomized clinical trials have shown that pharmacological therapy can reduce the risk of fractures. Read More

Eur J Cancer 2009 Dec 21;45(18):3205-12. Epub 2009 Oct 21.

Department of Endocrinology, Reproductive Medicine, and Osteoporosis, Philipps-University of Marburg, Baldingerstrasse, 35034 Marburg, Germany.

Introduction: The effects of doxorubicin/cyclophosphamide (A/C; 6 cycles) chemotherapy on bone mineral density (BMD), quantitative ultrasonography (QUS) and bone turnover markers in pre-menopausal women with oestrogen receptor-negative breast cancer (BC) were compared with age-matched controls.

Methods: Among 106 women (BC=53, controls=53), BMD (spine and hip), QUS (calcaneus and phalanges) and bone marker levels were measured at baseline, 6 and 12 months. Correlations between parameters were determined by Spearman's rho. Read More

J Bone Miner Res 2009 Apr;24(4):561-74

Colorado Center for Bone Research, Lakewood, Colorado 80227, USA.

Bone turnover markers (BTMs) have become increasingly important in the management of postmenopausal osteoporosis (PMO). In bisphosphonate-treated women with PMO, BTMs can provide early indications of treatment efficacy, are predictors of BMD response and fracture risk reduction, and are potentially useful for monitoring patient compliance. The bone resorption marker serum C-telopeptide cross-link of type 1 collagen (sCTX) has shown high sensitivity and specificity for the detection of increased bone resorption. Read More

Arthritis Res Ther 2009 26;11(1):R12. Epub 2009 Jan 26.

CombinatoRx, Incorporated, First Street, Cambridge, MA 02142, USA.

Introduction: Glucocorticoids are a mainstay of anti-inflammatory therapy, but significant adverse effects ultimately limit their utility. Previous efforts to design glucocorticoid structures with an increased therapeutic window have focused on dissociating anti-inflammatory transcriptional repression from adverse effects primarily driven by transcriptional activation. An alternative to this medicinal chemistry approach is a systems biology based strategy that seeks to amplify selectively the anti-inflammatory activity of very low dose glucocorticoid in immune cells without modulating alternative cellular networks that mediate glucocorticoid toxicity. Read More

Endocr Pract 2008 Dec;14(9):1102-7

Department of Endocrinology, Medwin Hospitals, Hyderabad, India.

Objective: To study the relationship between bone markers and bone mineral density (BMD) in an effort to identify their utility in postmenopausal women with osteoporosis.

Methods: Eighty-two consecutive postmenopausal women with untreated osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual-energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) and bone resorption (urinary free deoxypyridinoline) were measured in all patients. Read More

Nefrologia 2008 ;28 Suppl 3:67-78

H. Universitario de Canarias.

Unlabelled: With progression of chronic kidney disease (CKD), disorders of mineral metabolism appear. The classic sequence of events begins with a deficit of calcitriol synthesis and retention of phosphorus. As a result of this, serum calcium decreases and parathyroid hormone (PTH) is stimulated, producing in the bone the high turnover (HT) bone disease known as osteitis fibrosa while on the other extreme we find the forms of low turnover (LT) bone disease. Read More

Mol Diagn Ther 2008 ;12(3):157-70

INSERM Unit 664, Laënnec School of Medicine, Lyon, France.

Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in an increased risk of fracture. While the level of bone mass can be estimated by measuring bone mineral density (BMD) using dual X-ray absorptiometry (DXA), its measurement does not capture all the risk factors for fracture. Quantitative changes in skeletal turnover can be assessed easily and non-invasively by the measurement of serum and urinary biochemical markers; the most sensitive markers include serum osteocalcin, bone specific alkaline phosphatase, the N-terminal propeptide of type I collagen for bone formation, and the crosslinked C- (CTX) and N- (NTX) telopeptides of type I collagen for bone resorption. Read More

Ann Pharmacother 2008 Jul 27;42(7):1085-9. Epub 2008 May 27.

Harrison School of Pharmacy, Auburn University, AL, USA.

Objective: To review studies that investigated the use of once-yearly administered intravenous zoledronic acid for the treatment of postmenopausal osteoporosis.

Data Sources: Searches of MEDLINE (1966-February 2008) and EMBASE (1974-February 2008) were conducted using the terms zoledronic acid, once-yearly, and postmenopausal osteoporosis. Literature review was limited to human studies. Read More

Rev Clin Esp 2008 May;208(5):247-50

Departamento de Medicina Interna, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain.

Osteoporosis is a disease with high morbidity-mortality that is important because it predisposes to fractures. Thus, treatment of this disease is aimed at preventing them. However, and in spite of the fact that the fracture is the truly important consequence of therapeutic failure, it should not be considered to be an exponent of it given that it may be due to factors not related with lack of response such as intrinsic predisposition of the disease to development of fractures or being prone to falls. Read More

Crit Rev Clin Lab Sci 2008 ;45(2):221-58

Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, WA, Australia.

Biochemical markers of bone turnover (bone-turnover markers) are released during bone formation or resorption and can be measured in blood and/or urine. The concentration of bone-turnover markers in serum or urine reflect bone remodeling activity and can potentially be used as surrogate markers of the rate of bone formation or bone resorption. While the diagnosis of osteoporosis is based on bone mineral density (BMD), the absolute fracture risk for a particular BMD measurement varies several fold depending on age and is also influenced by other clinical risk factors. Read More

Eur J Intern Med 2008 Jan 26;19(1):51-6. Epub 2007 Nov 26.

University Hospital Insular, Department of Internal Medicine, Bone Metabolic Unit, University of Las Palmas de Gran Canaria, Investigation Group on Osteoporosis, Canary Islands, Spain.

Background: Daily doses higher than 7.5 mg/daily of prednisone or equivalents confer a great risk of vertebral and hip fractures with a clear dose dependence of fracture risk. Information regarding the utility in assessing trabecular bone mineral density by quantitative computer tomography (QCT) in these patients, either in the Canaries or in Spain, is lacking. Read More

Nihon Rinsho 2007 Nov;65 Suppl 9:259-63

Department of Orthopaedic Surgery, Kyorin University.

P R Health Sci J 2007 Jun;26(2):91-5

Endocrine Section, University of Puerto Rico, School of Medicine GPO Box 365067, San Juan, Puerto Rico 00936-5067.

Objective: Present evidence-based recommendations on the use of biochemical markers of bone turnover in the management of osteoporosis.

Methods: The English literature from 1999 to 2005 was reviewed by using data sources from MEDLINE.

Results: Measurement of biochemical markers of bone turnover helps us identify a high bone turnover rate. Read More

Ann N Y Acad Sci 2007 Nov 21;1117:258-63. Epub 2007 Jun 21.

Department of Orthopaedic Surgery, Medical College of Georgia, Institute of Molecular Medicine and Genetics, Augusta, Georgia 30912, USA.

An exciting new era in bone biology is a result of our greater understanding not only of the mechanisms of action of the medications we currently use for treatment of osteoporosis but also of the molecular pathways involved in normal and abnormal bone formation. In the coming years our increased understanding of these molecular pathways will result in many new medications for osteoporosis therapy. Together with the development of new drugs it will be necessary to develop better ways of assessing bone quality. Read More

Clin Chem Lab Med 2007 ;45(8):1014-8

Biochemistry Laboratory, General Hospital Jesenice, Jesenice, Slovenia.

Background: Recently published data identified bone-specific alkaline phosphatase (BALP) as a good marker of bone formation in different bone diseases and osteoporosis. Two methods are available for BALP determination: one measures enzyme activity, the other its mass concentration. We compared results for BALP activity and its mass concentration in a group of 88 healthy pre- and postmenopausal women to identify which is a more useful marker for detecting early menopausal bone remodelling changes. Read More

Clin Chem 2007 Jun 13;53(6):1109-14. Epub 2007 Apr 13.

Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Background: Plasma concentrations of procollagen peptides are decreased in osteogenesis imperfecta (OI), whereas other bone formation markers may be increased. We examined the utility of combining these markers in the diagnosis of OI in adults.

Methods: We measured plasma concentrations of procollagen-1 N-peptide (P1NP), osteocalcin, and bone alkaline phosphatase in 24 patients with nondeforming OI, 25 patients with low bone mass due to other causes, and 38 age- and sex-matched controls. Read More

Osteoporos Int 2007 Jun 18;18(6):733-41. Epub 2007 Jan 18.

Graduate School of Public Health, University of Pittsburgh, PA 15261, USA.

Unlabelled: Individual-specific percent European ancestry was assessed in 1,277 African Americans. We found significant correlations between proportion of European ancestry and several musculoskeletal traits, indicating that admixture mapping may be a useful strategy for locating genes affecting these traits.

Introduction: Genotype data for admixed populations can be used to detect chromosomal regions influencing disease risk if allele frequencies at disease-related loci differ between parental populations. Read More

Am J Hematol 2007 Mar;82(3):185-91

Department of Medical Oncology, Hacettepe University Institute of Oncology, and Biochemistry Laboratory, Hacettepe University Ihsan Dogramaci Children's Hospital, Ankara, Turkey.

This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Read More

Eur J Clin Pharmacol 2006 Oct 16;62(10):781-92. Epub 2006 Aug 16.

Nordic Bioscience Diagnostics A/S, 2730, Herlev, Denmark.

Background: Maintenance of the structural and functional integrity of the skeleton is a critical function of a continuous remodeling driven by highly associated processes of bone resorption and synthetic activities driven by osteoclasts and osteoblasts, respectively. Acceleration of bone turnover, accompanied with a disruption of the coupling between these cellular activities, plays an established role in the pathogenesis of metabolic bone diseases, such as osteoporosis. During the past decades, major efforts have been dedicated to the development and clinical assessment of biochemical markers that can reflect the rate of bone turnover. Read More

J Clin Endocrinol Metab 2005 Nov 16;90(11):6323-31. Epub 2005 Aug 16.

Academic Unit of Bone Metabolism, University of Sheffield, Sheffield S5 7AU, United Kingdom.

Context: The discovery of the receptor activator for nuclear factor kappaB (RANK) ligand (RANKL)/RANK signaling pathway has marked a major advance in our understanding of the mechanisms controlling osteoclastogenesis. RANKL, expressed by preosteoblasts and stromal cells, binds to RANK, expressed by cells of the osteoclast lineage, inducing a signaling cascade leading to the differentiation and fusion of osteoclast precursor cells and stimulating the activity of the mature osteoclast. The effects of RANKL are counteracted by osteoprotegerin (OPG), a soluble neutralizing decoy receptor. Read More