Bone Modulation Strategies for the Prevention of Osteoporosis-Associated Fractures

The global burden of osteoporosis is enormous; an estimated 9 million osteoporotic fractures occur annually, of which more than 1.5 million are reported in the United States alone.^1,2  Approximately 1 in 2 fractures among women and 1 in 5 among men over age 50 will be associated with osteoporosis.³ The mortality rates from these fractures are high; approximately 15% of women and 30% of men who experience an osteoporosis-related hip fracture will die from consequences due to the injury and many others will have poor outcomes.¹ The US Surgeon General’s Report on Bone Health and Osteoporosis from 2012 estimates that by the year 2020, in the absence of lifestyle changes, 50% of the American population over the age of 50 will have bone loss leading to osteoporosis.²

A number of factors contribute to the lifetime risk for an osteoporotic fracture. The most significant cause of bone loss is the reduction of circulating estrogen from menopause in women, which can also be triggered by surgical oophorectomy, drug therapies including Depo-Provera for contraception or aromatase inhibitors for breast cancer, or glucocorticoids. In men, low testosterone carries a similar risk.³ Anorexia, cigarette smoking, excessive alcohol consumption, and a sedentary lifestyle are also contributing risk factors. White and Asian populations are also at higher risk than other races.

Risk factors for fracture associated with bone loss include a previous history of fracture and/or a similar fracture in a first-degree relative, and most prominently, a low bone mineral density (BMD). The World Health Organization (WHO) developed the FRAX prediction tool for calculating 10-year risk of fracture. The FRAX tool uses the previously identified risk factors,  along with femoral neck BMD assessments and body mass index (BMI) to identify candidates for interventions.  Likewise, in its 2008 guidelines, the National Osteoporosis Foundation (NOF) recommended initiating therapy for people based on the same risk factors and having a FRAX-based 10-year risk of at least 3% for a hip fracture or 20% for another osteoporotic fracture.³

Understanding the Role of BMI in Fractures

People of low body mass have traditionally been considered to have higher fracture risk due to the association between low BMI and BMD; therefore, it was often presumed that being overweight or even obese conferred some protection from osteoporosis. However, this protective effect appears to be mitigated by a higher risk of falling due to deconditioning. A recent investigation by Poiana et al⁴ of 622 menopausal women in Romania sought to examine the correlation between weight and fracture in high-risk women, one-third (39.22%) of whom were obese (BMI ≥ 30 kg/m²). The fracture prevalence was found to be lower in the obese group compared with nonobese women (1.35% vs 1.67%), supporting a possible protective role of higher BMI in fracture risk.  However, although BMI positively correlated with BMD, the investigators concluded that the evidence was insufficient to say that obesity was protective of all types of fractures. ⁴