2019 Update on bone health

OBG Management. 2019 December;31(12):16-21

December 5, 2019|OBG Management

In this Update: BMD testing—understanding who to scan and what sites to evaluate, ospemifene’s effects on bone, assessing for sarcopenia as well as osteoporosis, and aromatase inhibitors and treatment for fracture prevention

Dyspareunia drug has positive effects on bone

de Villiers TJ, Altomare C, Particco M, et al. Effects of ospemifene on bone in postmenopausal women. Climacteric. 2019;22:442-447.

Ospemifene is a selective estrogen receptor modulator (SERM), given daily and orally, that was approved by the US Food and Drug Administration (FDA) in 2013 for moderate to severe dyspareunia due to menopause-related vulvovaginal atrophy (VVA). More recently, the indication has been extended to include vaginal dryness of menopause. Other SERMs have shown efficacy in prevention and treatment of osteoporosis, including raloxifene, which was FDA approved for the respective indications in 1997 and 1999, and lasofoxifene, which showed efficacy but was not approved in the United States.²

Previously, ospemifene effectively reduced bone loss in ovariectomized rats, with activity comparable to that of estradiol and raloxifene.³ Clinical data from 3 phase 1 or 2 clinical trials found that ospemifene 60 mg/day had a positive effect on biochemical markers for bone turnover in healthy postmenopausal women, with significant improvements relative to placebo and effects comparable to those of raloxifene.⁴

Effects on bone formation/resorption biomarkers

In a recent study, de Villiers and colleagues reported the first phase 3 trial that looked at markers of bone formation and bone resorption.⁵ A total of 316 women were randomly assigned to receive ospemifene, and 315 received placebo.

Demographic and baseline characteristics were similar between treatment groups. Participants' mean age was approximately 60 years, mean body mass index (BMI) was 27.2 kg/m2, and mean duration of VVA was 8 to 9 years. Serum levels of 9 bone biomarkers were similar between groups at baseline.

At week 12, all 5 markers of bone resorption improved with ospemifene treatment, and 3 of the 5 (NTX, CTX, and TRACP-5b) did so in a statistically significant fashion compared with placebo (P≤.02). In addition, at week 12, all 4 markers of bone formation improved with ospemifene treatment compared with placebo (P≤.008). Furthermore, lower bone resorption markers with ospemifene were observed regardless of time since menopause (≤ 5 years or
> 5 years) or baseline BMD, whether normal, osteopenic, or osteoporotic.

Interpret results cautiously

The authors caution that the data are limited to biochemical markers rather than fracture or BMD. It is known that there is good correlation between biochemical markers for bone turnover and the occurrence of fracture.⁶

WHAT THIS EVIDENCE MEANS FOR PRACTICE

Ospemifene is an oral SERM approved for the treatment of moderate to severe dyspareunia as well as dryness from VVA due to menopause. The preclinical animal data and human markers of bone turnover all support the antiresorptive action of ospemifene on bones. Thus, one may safely surmise that ospemifene's direction of activity in bone is virtually indisputable. The magnitude of that activity is, however, unstudied. Therefore, when choosing an agent to treat women with dyspareunia or vaginal dryness from VVA of menopause, determining any potential add-on benefit in bone may be appropriate for that particular patient, although one would not use it as a stand-alone agent for bone only.

Continue to: Sarcopenia adds to osteoporotic risk for fractures...

References

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