For which of my patients is this treatment appropriate?
Steven R. Goldstein, MD
Dr. Goldstein is Professor, Department of Obstetrics and Gynecology, at New York University School of Medicine, and Director, Gynecologic Ultrasound, and Co-Director, Bone Densitometry and Body Composition, at New York University Medical Center, in New York, New York. He serves on the OBG Management Board of Editors.
Dr. Goldstein reports that he is on the Gynecology Advisory Boards of JDS Therapeutics, Pfizer, Shionogi, and Teva; a consultant to Cook Ob/Gyn, Philips Ultrasound, and Smith & Nephew; and a speaker for JDS Therapeutics, Noven, Pfizer, and Shionogi.
A new agent, and new understandings of old drugs, top the year’s developments in bone health
Gynecologists are “first-line” providers for the diagnosis and treatment of osteoporosis in women. Lest you doubt the importance of this fact, consider that there are more osteoporotic fractures annually in the United States than all myocardial infarctions, strokes, breast cancers, and gynecologic malignancies combined. It is our duty to stay abreast of current developments in the diagnosis and treatment of this potentially devastating skeletal disorder as our patients live longer and longer.
In this article, I present recent studies on:
FIRST TISSUE-SELECTIVE ESTROGEN COMPLEX PROTECTS AGAINST BONE LOSS WITHOUT AFFECTING ENDOMETRIAL AND BREAST TISSUE
Komm BS, Mirkin S, Jenkins SN. Development of conjugated estrogens/bazedoxifene, the first tissue selective estrogen complex (TSEC) for management of menopausal hot flashes and postmenopausal bone loss. Steroids. 2014;90:71–81.
Pinkerton JV, Harvey JA, Lindsay R, et al; SMART-5 Investigators. Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a randomized trial. J Clin Endocrinol Metab. 2014;99(2):e189–e198.
Conjugated estrogens combined with the selective estrogen receptor modulator (SERM) bazedoxifene (Duavee) are a new option to alleviate menopausal symptoms and prevent postmenopausal bone loss. The rationale for development of the tissue-selective estrogen complex (TSEC) was to combine the benefits of conjugated estrogens with the SERM’s ability to offset estrogenic stimulation of the endometrium and breast.
TSECs offer a progestin-free alternative to traditional hormone therapy for women with a uterus. In preclinical studies, investigators found evidence to support bazedoxifene as the SERM of choice and demonstrated that, by combining it with conjugated estrogens, they could provide an optimal balance of estrogen-receptor agonist/antagonist activity, compared with other potential TSEC pairings. Clinical study results confirmed the efficacy of this combination in maintaining bone mass.
Given separately, conjugated estrogens and bazedoxifene each protect against the loss of BMD and help prevent fracture in postmenopausal women.
Findings in key populations
Komm and colleagues describe substudies of the Selective estrogens, Menopause, and Response to Therapy (SMART) trials to evaluate the combination of conjugated estrogens and SERMs to prevent osteoporosis in postmenopausal women with a uterus. One SMART-1 trial included two osteoporosis prevention substudies that evaluated the combination of conjugated estrogens and bazedoxifene in different subpopulations:
All doses of conjugated estrogens and bazedoxifene significantly increased the adjusted mean percentage of change in BMD of the lumbar spine from baseline to 24 months (a primary endpoint), compared with placebo, which was associated with decreases in BMD (P<.001). Findings were similar for total hip BMD.
In a separate study, Pinkerton and colleagues found that the dose of conjugated estrogens (0.45 mg) and bazedoxifene (20 mg) approved by the US Food and Drug Administration does not cause a change in breast density or thickness of the endometrium, nor does it increase breast pain, compared with placebo.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
This newly available TSEC—a combination of conjugated estrogens (0.45 mg) and bazedoxifene (20 mg)—is an effective, well-tolerated alternative to traditional estrogen-progestin hormone therapy for relief of menopausal symptoms and prevention of osteoporosis in postmenopausal women with a uterus.
DON’T EXCLUDE SUNLIGHT FROM THE BONE–HEALTH EQUATION
Holick MF. Sunlight, ultraviolet radiation, vitamin D, and skin cancer: how much sunlight do we need? Adv Exp Med Biol. 2014;810:1–16.
Many people think of vitamin D as the “sunshine vitamin.” During exposure to sunlight, ultraviolet photons enter the skin and convert 7-dehydrocholesterol to previtamin D3, which, in turn, is converted to vitamin D3.
Throughout most of human history, people have depended on sunlight for vitamin D. Variables such as skin pigmentation, sunscreen use, aging, time of day, season, and latitude dramatically affect previtamin synthesis.
Although vitamin D deficiency was thought to have been conquered, it is now recognized that more than 50% of the world’s population is at risk for vitamin D insufficiency or low levels of 25-hydroxyvitamin D. Among the reasons are inadequate fortification of foods with vitamin D and a misconception that most balanced diets contain adequate vitamin D.
For which of my patients is this treatment appropriate?
A peer-to-peer audiocast with JoAnn Pinkerton, MD, and Anne Moore, DNP, APN
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