Pharmacological Therapy of Osteoporosis: A Systematic Current Review of Literature

This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians.

Osteoporotic fractures are a significant public health problem, resulting in substantial morbidity and mortality. Previous estimates of the economic burden of osteoporosis, however, have not fully accounted for the costs associated with treatment of nonhip fractures, minority populations, or men. Accordingly, the 1995 total direct medical expenditures for the treatment of osteoporotic fractures were estimated for all persons aged 45 years or older in the United States by age group, sex, race, type of fracture, and site of service (inpatient hospital, nursing home, and outpatient). Osteoporosis attribution probabilities were used to estimate the proportion of health service utilization and expenditures for fractures that resulted from osteoporosis. Health care expenditures attributable to osteoporotic fractures in 1995 were estimated at $13.8 billion, of which $10.3 billion (75.1%) was for the treatment of white women, $2.5 billion (18.4%) for white men, $0.7 billion (5.3%) for nonwhite women, and $0.2 billion (1.3%) for nonwhite men. Although the majority of U.S. health care expenditures for the treatment of osteoporotic fractures were for white women, one-fourth of the total was borne by other population subgroups. By site-of-service, $8.6 billion (62.4%) was spent for inpatient care, $3.9 billion (28.2%) for nursing home care, and $1.3 billion (9.4%) for outpatient services. Importantly, fractures at skeletal sites other than the hip accounted for 36.9% of the total attributed health care expenditures nationally. The contribution of nonhip fractures to the substantial morbidity and expenditures associated with osteoporosis has been underestimated by previous researchers.

Objectives To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). Methods In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. Results Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. Conclusions Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. Trial registration number JapicCTI-101263.