Clinical Review

Update on Osteoporosis

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Ziglar and Hunter concluded that the use of OCs containing 20 µg EE prevents adolescents and young women from attaining peak BMD. Evidence on the effect of contraceptives formulated with 30 to 35 µg EE is less definitive, but this dose may also impede BMD acquisition in adolescents.

To ensure breast health and reduce the risk of venous thromboembolic events, drug makers have developed OCs with lower and lower doses of EE. In the process, however, the beneficial effects of endogenous estradiol on bone acquisition have been suppressed. Therefore, the lowest-dose OC may not necessarily be the most appropriate clinical choice for adolescents and young women seeking contraception.

Related Article: Osteoporosis treatment and breast cancer prevention: Two goals, one treatment? Robert L. Barbieri, MD (Editorial, November 2013)


Brixen K, Chapurlat R, Cheung AM, et al. Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab. 2013;98(2):571–580.

Current treatments for osteoporosis include antiresorptive agents, such as bisphosphonates and denosumab, that preserve bone mass by reducing the rate of bone turnover. These drugs reduce the number or activity (or both) of bone-resorbing osteoclasts. Because osteoclasts play a role in stimulating bone formation by osteoblasts, these treatments indirectly lower bone formation.

Odanacatib is a drug in Phase 3 development for the treatment of postmenopausal osteoporosis. It is a highly selective and reversible oral inhibitor of the collagenase activity of cathepsin K, which is secreted by osteoclasts. Odanacatib reduces bone resorption without reducing the number of osteoclasts and, thus, appears to preserve bone formation.

Details of the trial
Brixen and colleagues conducted a randomized, double-blind, international, 2-year, Phase 3 trial comparing odancatib 50 mg once weekly with placebo in postmenopausal women treated with calcium and vitamin D. The primary endpoint was the change from baseline BMD at the lumbar spine at 1 year, as assessed by DXA. Secondary endpoints included the change from baseline BMD at the hip (total hip, femoral neck, and trochanter) at 1 year, the change from baseline BMD at the spine and hip at 2 years, and 1- and 2-year changes in bone-turnover markers. A total of 214 women were enrolled (average age: 64 years; average T-score of 1.8 at the lumbar spine, –1.8 at the femoral neck, and –1.3 at the total hip).

At 1 year, the change from baseline BMD at the lumbar spine was significantly higher (P <.001) in women receiving odanacatib, compared with placebo (treatment difference: 3.5%). At 2 years, the treatment difference was even higher (5.4%). The mean changes in BMD at the femoral neck, total hip, and trochanter also were significantly greater (P <.001) in women receiving odanacatib, with treatment differences at 2 years of 3.8%, 3.3%, and 5.5%, respectively.

During the first 6 months of the trial, serum concentrations of bone-turnover markers (CTX and P1NP) decreased significantly (P <.001) in odanacatib-treated women, compared with those given placebo.

Although no new agents for the treatment of osteoporosis have been introduced over the past year, cathepsin K inhibitors appear to offer great promise for the future. As clinicians, we need to keep abreast of new developments that may be of potential value to our patients.


Cohen A, Stein EM, Recker RR, et al. Teriparatide for idiopathic osteoporosis in premenopausal women: A pilot study. J Clin Endocrinol Metab. 2013;98(5):1971–1981.

Idiopathic osteoporosis (IOP) affects young, otherwise healthy men and women with intact gonadal function and no secondary cause of bone loss or fragility. Women with IOP have abnormal bone microarchitecture with thinner cortices; fewer, thinner, and more widely separated and heterogeneously distributed trabeculae; more rod-like trabecular structures; less trabecular stiffness; and a higher level of marrow fat.

The osteoanabolic agent teriperatide increases BMD and reduces the incidence of fracture in postmenopausal women and in patients with glucocorticoid-induced osteoporosis, and it increases BMD in men with IOP. This study explored its effect in premenopausal women with IOP.

Details of the study
Cohen and colleagues recruited premenopausal women aged 20 to 48 years who had one or both of the following traits:

  • a history of at least one low-trauma fracture more than 6 months before enrollment
  • low BMD of the spine or hip (Z-score of –2.0 or below), as assessed by DXA.

All participants had regular menses and early follicular-phase follicle-stimulating hormone (FSH) levels below 20 mIU/mL; none were using hormonal contraception. Women who had secondary osteoporosis related to estrogen deficiency, an eating disorder, an endocrinopathy, celiac or gastrointestinal disease, hyperparathyroidism, marked hypercalciuria, a low serum level of 25-hydroxyvitamin D (<20 ng/mL), and drug exposures were excluded.

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