Bone Health: 3 New Things

Nov 15, 2018

(1) Exercise limits bone loss but not weight gain; (2) BMD may serve as a biomarker; (3) men are at high risk for secondary fractures.

References:

1. Kohrt W. Bioenergetic and metabolic consequences of the loss of ovarian function in women. Presented at: 2018 American Physiological Society Conference: Cardiovascular, Renal and Metabolic Diseases: Sex-Specific Implications for Physiology; October 1, 2018; Knoxville, TN.2. Black DE, et al. Change in BMD as a Surrogate for Fracture Risk Reduction in Osteoporosis Trials: Results from Pooled, Individual-level Patient Data from the FNIH Bone Quality Project. Presented at: American Society for Bone and Mineral Research 2018 Annual Meeting; October 1, 2018; Orlando, FL. Abstract 1070.3. Morin SN, Yan L, Lix LM, Leslie WD. Changes in the Risk of Subsequent Major Osteoporotic Fractures over Time in Men and Women: A Population-Based Observational Study With 25-Year Follow-up. Presented at: American Society for Bone and Mineral Research 2018 Annual Meeting; September 29, 2018; Orlando, FL. Abstract 1038.

The highlights of three new studies in bone health include: (1) exercise minimizes changes in bone density when estrogen levels decrease; (2) bone mineral density (BMD) changes after 2 years of osteoporosis drug therapy could serve as a surrogate biomarker for reduced fracture risk; and (3) men have a high risk of secondary osteoporotic fractures.^1-3 Scroll through the slides for the latest findings and their clinical implications.

A prospective study randomized 66 women, aged 45 to 50 years, with normal menstrual cycle function to receive 6 months of gonadotropin-releasing hormone (GnRH) agonist, GnRH agonist plus supervised resistance exercise, or placebo. The estrogen supplement groups were compared with ovarian suppression control groups who did not receive hormone therapy but were matched for exercise status. Bone loss was measured through dual-energy x-ray absorptiometry scans and energy expenditure through doubly labeled water.

All of the participants had a slower metabolism, burned fewer calories, and showed a decrease in muscle mass and an accumulation of abdominal fat due to the loss of ovarian function. These symptoms were prevented by estrogen therapy. Those who exercised were protected against the decrease in bone density but not changes in the other symptoms.¹

Clinical Implications: “Our findings suggest that exercise can attenuate some (loss of bone), but not all (decline in resting metabolic rate) of the consequences of ovarian hormone suppression,” stated the researchers, led by Wendy Kohrt, PhD, associate director of the Center for Women's Health and professor of medicine at the University of Colorado, Denver School of Medicine, in Denver, CO.

A large pooled analysis of 22 clinical trials found that 24-month percentage change in dual-energy x-ray absorptiometry (DXA) BMD explained a large proportion of the fracture risk reduction across a range of osteoporosis treatments. The osteoporosis drugs in this meta-analysis included bisphosphonates, selective estrogen receptor modulators, estrogen, odanacatib, denosumab, parathyroid hormone (PTH1-34), and abaloparatide (PTH1-84). The 83,395 subjects with DXA scans had 4515 vertebral, 6608 non-vertebral, and 873 hip fractures.

The percentage difference in increase in BMD (change in BMD with treatment minus the change in BMD with placebo) in femoral neck BMD was 65% for vertebral fractures, 74% for non-vertebral fractures, and 65% for hip fractures. The results were similar for total hip, but the percentage difference increase in BMD was lower for lumbar spine BMD.²

Clinical Implications: “Our results indicate that changes in total hip and femoral neck BMD explain a large proportion of the treatment-related reduction in fracture risk for all 3 fracture types. Importantly, this analysis included therapies with diï¬ering mechanisms of action. These data, along with others generated from this project, support the potential value of DXA BMD change as a surrogate for fractures in future trials,” stated the researchers, led by Dennis M. Black, PhD, of the University of California, San Francisco.

A matched historical cohort study identified 29,694 index cases (11,028 wrist; 9313 hip; 5799 humerus; 3554 spine). The annual crude rate of subsequent major osteoporotic fracture per 1000 person-years among cases was 18.5 in men and 29.6 in women. Rate ratios across all follow-up years were 2.5 in men and 1.6 in women compared with controls.³

Hazard ratios for subsequent major osteoporotic fracture were higher in men than women, particularly in the first year following the index fracture, and remained very high for men during the first 3 years of follow-up.

Clinical Implications: “The risk of subsequent major osteoporotic fracture was elevated in both sexes over 25 years of follow-up with time-dependent attenuation that was most evident in men. These results underscore the importance of timely recognition of fracture events, especially in men, a population in whom secondary prevention is vastly under-implemented,” stated the researchers, led by Suzanne Morin, MD, of McGill University in Montreal, Quebec, Canada.

Sources

Exercise Reduces Osteoporosis in Ovarian Function Loss

BMD Improvements Act as Surrogate for Fracture Risk

Risk of Secondary Osteoporotic Fractures High in Men