Clinical Review

2019 Update on bone health

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

References

International Society for Clinical Densitometry. 2019 ISCD Official Positions-Adult. June 2019. https://www.iscd.org/official-positions/2019-iscd-official-positions-adult. Accessed November 22, 2019.
Goldstein SR, Neven P, Cummings S, et al. Postmenopausal evaluation and risk reduction with lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause. 2011;18:17-22.
Kangas L, Unkila M. Tissue selectivity of ospemifene: pharmacologic profile and clinical implications. Steroids. 2013;78:1273-1280.
Constantine GD, Kagan R, Miller PD. Effects of ospemifene on bone parameters including clinical biomarkers in postmenopausal women. Menopause. 2016;23:638-644.
de Villiers TJ, Altomare C, Particco M, et al. Effects of ospemifene on bone in postmenopausal women. Climacteric. 2019;22:442-447.
Gerdhem P, Ivaska KK, Alatalo SL, et al. Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res. 2004;19:386-393.
Siris ES, Adler R, Bilezikian J, et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int. 2014;25:1439-1443.
Epidemiologic and methodologic problems in determining nutritional status of older persons. Proceedings of a conference. Albuquerque, New Mexico, October 19-21, 1988. Am J Clin Nutr. 1989;50(5 suppl):1121-1235.
Drey M, Sieber CC, Bertsch T, et al. Osteosarcopenia is more than sarcopenia and osteopenia alone. Aging Clin Exp Res. 2016;28:895-899.
Lima RM, de Oliveira RJ, Raposo R, et al. Stages of sarcopenia, bone mineral density, and the prevalence of osteoporosis in older women. Arch Osteoporos. 2019;14:38.
Mathias S, Nayak U, Isaacs B. Balance in elderly patients: the "get-up and go" test. Arch Phys Med Rehabil. 1986;67:387-389.
Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol. 2014;32:2255-2269.
Schmidt N, Jacob L, Coleman R, et al. The impact of treatment compliance on fracture risk in women with breast cancer treated with aromatase inhibitors in the United Kingdom. Breast Cancer Res Treat. 2016;155:151-157.
Neuner JM, Shi Y, Kong AL, et al. Fractures in a nationwide population-based cohort of users of breast cancer hormonal therapy. J Cancer Surviv. 2018;12:268-275.
Goldstein SR. 2015 Update on osteoporosis. OBG Manag. 2015;27:31-39.
Majithia N, Atherton PJ, Lafky JM, et al. Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year follow-up. Support Care Cancer. 2016;24:1219-1226.
Gnant M, Pfeiler G, Dubsky PC, et al; Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in breast cancer (ABCSG-18): a multicenter, randomized, double-blind, placebo-controlled trial. Lancet. 2015;386:433-443.
Leslie WD, Morin SN, Lix LM, et al. Fracture risk in women with breast cancer initiating aromatase inhibitor therapy: a registry-based cohort study. Oncologist. 2019;24:1432-1438.

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

International Society for Clinical Densitometry. 2019 ISCD Official Positions-Adult. June 2019. https://www.iscd.org/official-positions/2019-iscd-official-positions-adult. Accessed November 22, 2019.
Goldstein SR, Neven P, Cummings S, et al. Postmenopausal evaluation and risk reduction with lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause. 2011;18:17-22.
Kangas L, Unkila M. Tissue selectivity of ospemifene: pharmacologic profile and clinical implications. Steroids. 2013;78:1273-1280.
Constantine GD, Kagan R, Miller PD. Effects of ospemifene on bone parameters including clinical biomarkers in postmenopausal women. Menopause. 2016;23:638-644.
de Villiers TJ, Altomare C, Particco M, et al. Effects of ospemifene on bone in postmenopausal women. Climacteric. 2019;22:442-447.
Gerdhem P, Ivaska KK, Alatalo SL, et al. Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res. 2004;19:386-393.
Siris ES, Adler R, Bilezikian J, et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int. 2014;25:1439-1443.
Epidemiologic and methodologic problems in determining nutritional status of older persons. Proceedings of a conference. Albuquerque, New Mexico, October 19-21, 1988. Am J Clin Nutr. 1989;50(5 suppl):1121-1235.
Drey M, Sieber CC, Bertsch T, et al. Osteosarcopenia is more than sarcopenia and osteopenia alone. Aging Clin Exp Res. 2016;28:895-899.
Lima RM, de Oliveira RJ, Raposo R, et al. Stages of sarcopenia, bone mineral density, and the prevalence of osteoporosis in older women. Arch Osteoporos. 2019;14:38.
Mathias S, Nayak U, Isaacs B. Balance in elderly patients: the "get-up and go" test. Arch Phys Med Rehabil. 1986;67:387-389.
Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol. 2014;32:2255-2269.
Schmidt N, Jacob L, Coleman R, et al. The impact of treatment compliance on fracture risk in women with breast cancer treated with aromatase inhibitors in the United Kingdom. Breast Cancer Res Treat. 2016;155:151-157.
Neuner JM, Shi Y, Kong AL, et al. Fractures in a nationwide population-based cohort of users of breast cancer hormonal therapy. J Cancer Surviv. 2018;12:268-275.
Goldstein SR. 2015 Update on osteoporosis. OBG Manag. 2015;27:31-39.
Majithia N, Atherton PJ, Lafky JM, et al. Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year follow-up. Support Care Cancer. 2016;24:1219-1226.
Gnant M, Pfeiler G, Dubsky PC, et al; Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in breast cancer (ABCSG-18): a multicenter, randomized, double-blind, placebo-controlled trial. Lancet. 2015;386:433-443.
Leslie WD, Morin SN, Lix LM, et al. Fracture risk in women with breast cancer initiating aromatase inhibitor therapy: a registry-based cohort study. Oncologist. 2019;24:1432-1438.

Bisphosphonates turn 50

2019 Update on bone health

References

Dyspareunia drug has positive effects on bone

Effects on bone formation/resorption biomarkers

Interpret results cautiously

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