Biochemical Markers of Bone Turnover, Hip Bone Loss, and Fracture in Older Men: The MrOS Study

We used data from the Osteoporotic Fractures in Men (MrOS) study to test the hypothesis that men with higher levels of bone turnover would have accelerated bone loss and an elevated risk of fracture. MrOS enrolled 5995 subjects >65 yr; hip BMD was measured at baseline and after a mean follow‐up of 4.6 yr. Nonspine fractures were documented during a mean follow‐up of 5.0 yr. Using fasting serum collected at baseline and stored at −190°C, bone turnover measurements (type I collagen N‐propeptide [PINP]; β C‐terminal cross‐linked telopeptide of type I collagen [βCTX]; and TRACP5b) were obtained on 384 men with nonspine fracture (including 72 hip fractures) and 947 men selected at random. Among randomly selected men, total hip bone loss was 0.5%/yr among those in the highest quartile of PINP (>44.3 ng/ml) and 0.3%/yr among those in the lower three quartiles (p = 0.01). Fracture risk was elevated among men in the highest quartile of PINP (hip fracture relative hazard = 2.13; 95% CI: 1.23, 3.68; nonspine relative hazard = 1.57, 95% CI: 1.21, 2.05) or βCTX (hip fracture relative hazard = 1.76, 95 CI: 1.04, 2.98; nonspine relative hazard = 1.29, 95% CI: 0.99, 1.69) but not TRACP5b. Further adjustment for baseline hip BMD eliminated all associations between bone turnover and fracture. We conclude that higher levels of bone turnover are associated with greater hip bone loss in older men, but increased turnover is not independently associated with the risk of hip or nonspine fracture.

[1]  P. Garnero,et al.  New automated multiplex assay for bone turnover markers in osteoporosis. , 2008, Clinical chemistry.

[2]  P. Delmas,et al.  Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis , 2008, Osteoporosis International.

[3]  P. Ebeling Clinical practice. Osteoporosis in men. , 1999, The New England journal of medicine.

[4]  P. Delmas,et al.  High bone turnover is associated with accelerated bone loss but not with increased fracture risk in men aged 50 and over: the prospective MINOS study , 2007, Annals of the rheumatic diseases.

[5]  P. Garnero,et al.  Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. , 2008, Clinical chemistry.

[6]  J. Rissanen,et al.  Secreted Tartrate-Resistant Acid Phosphatase 5b is a Marker of Osteoclast Number in Human Osteoclast Cultures and the Rat Ovariectomy Model , 2008, Calcified Tissue International.

[7]  J. Kaufman,et al.  Biochemical assessment of bone turnover and bone fragility in men , 2007, Osteoporosis International.

[8]  S. Cummings,et al.  Predictors of Non‐Spine Fracture in Elderly Men: The MrOS Study , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  O. Johnell,et al.  Free Testosterone is an Independent Predictor of BMD and Prevalent Fractures in Elderly Men: MrOS Sweden , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  S. Cummings,et al.  Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study--a large observational study of the determinants of fracture in older men. , 2005, Contemporary clinical trials.

[11]  P. Cawthon,et al.  Overview of recruitment for the osteoporotic fractures in men study (MrOS). , 2005, Contemporary clinical trials.

[12]  J. Eisman,et al.  Bone Resorption and Osteoporotic Fractures in Elderly Men: The Dubbo Osteoporosis Epidemiology Study , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[13]  R. Eastell,et al.  Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption , 1993, Osteoporosis International.

[14]  P. Delmas,et al.  Role of sex steroids in the regulation of bone morphology in men. The MINOS study , 2004, Osteoporosis International.

[15]  Anders Isaksson,et al.  Biochemical Markers of Bone Metabolism and Prediction of Fracture in Elderly Women , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  Jacques P. Brown,et al.  Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment. , 2004, Clinical therapeutics.

[17]  Kani Chen,et al.  Generalized case–cohort sampling , 2001 .

[18]  P. Delmas,et al.  Biochemical Markers of Bone Turnover, Endogenous Hormones and the Risk of Fractures in Postmenopausal Women: The OFELY Study , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[19]  R. Eastell,et al.  Preanalytical Variability of Biochemical Markers of Bone Turnover , 2000, Osteoporosis International.

[20]  M. Seibel,et al.  Molecular Markers of Bone Turnover: Biochemical, Technical and Analytical Aspects , 2000, Osteoporosis International.

[21]  W E Barlow,et al.  Analysis of case-cohort designs. , 1999, Journal of clinical epidemiology.

[22]  P. Delmas,et al.  Markers of Bone Turnover Predict Postmenopausal Forearm Bone Loss Over 4 Years: The OFELY Study , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[23]  S. Cummings,et al.  Biochemical Markers of Bone Turnover and Prediction of Hip Bone Loss in Older Women: The Study of Osteoporotic Fractures , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  E. Seeman,et al.  Osteoporosis in Men , 1999, Osteoporosis International.

[25]  B. L. Riggs,et al.  A Unitary Model for Involutional Osteoporosis: Estrogen Deficiency Causes Both Type I and Type II Osteoporosis in Postmenopausal Women and Contributes to Bone Loss in Aging Men , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.