As the Baby Boomer generation – and everyone else – gets older, the prevalence of bone-related conditions will continue to increase, disproportionately affecting women. New research shows that hormone therapy for menopause has a beneficial effect on bone strength.
According to the Endocrine Society’s 2016 Endocrine Facts and Figures Report on Bone and Mineral, more than 34 million people in the U.S. have low bone mineral density (BMD), and another 10 million or more have osteoporosis. For women, the picture is particularly bleak, as 80% of osteoporosis diagnoses are for women, and women are three times more likely than men to have an osteoporosis-related fracture. This is at least partly because menopause hastens the rate at which women lose bone mass, creating an imbalance between bone resorption and formation and leading to a net loss, which sets the stage for osteoporosis to develop. Importantly, although BMD is a major determinant of bone strength and fracture risk, half of fragility fractures occur in those with BMD values in the osteopenic or normal range, suggesting that bone microarchitecture also affects bone strength.
As the global population ages and life expectancy continues to inch upward, the prevalence of age-related conditions like osteopenia and osteoporosis will only increase. Yet, these conditions will lead to occurrence of fractures, which in their turn can markedly impact quality of life by reducing mobility as well as be prohibitively expensive to manage, especially when assisted living or long-term nursing home care is required.
BMD is known to be improved by menopausal hormone therapy (MHT), which can be a combination of progesterone/estrogen or only estrogen therapy, is generally given to ameliorate vasomotor symptoms and vaginal dryness; however, in 2005, when results from the Women’s Health Initiative trial showed increased risk of blood clots, heart disease, stroke, and breast cancer in some women taking MHT, MHT use became somewhat controversial. Since that time, medical organizations including the Endocrine Society have issued statements indicating their consensus that, for most healthy, recently menopausal women, MHT is safe to use for a period of within 10 years of menopause. Such organizations have also stipulated that MHT should be individualized, taking into consideration such factors as quality of life priorities as well as the degree of each woman’s personal risk.
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A new study might even have the as-yet-unconverted looking at MHT with fresh eyes. Georgios Papadakis, MD, of the Lausanne University Hospital in Switzerland and his team of researchers are the first to have investigated whether MHT’s positive effects on BMD extend to bone microarchitecture. The team used data gathered from the ongoing OsteoLaus Cohort Study, certain results of which were published in 2012. OsteoLaus was designed to identify women at high risk for fracture based on clinical risk factors for osteoporosis, bone ultrasound of the heel, lumbar spine and hip BMD, assessment of vertebral fracture by dual x-ray absorptiometry (DXA), and microarchitecture evaluation by trabecular bone score (TBS). Results showed that TBS can be used to predict fracture risk in postmenopausal women, independently of BMD and the Fracture Risk Assessment tool.
“I think the real question is if there is a place for MHT as an osteoporosis treatment. Maybe we start to think of MHT as a first-choice treatment for young postmenopausal women.” – Georgios Papadakis, MD, Lausanne University Hospital, Switzerland
OsteoLaus included 1,500 Swiss women aged 50 to 80 years, but any who had undergone bone-modulating treatments were excluded from Papadakis and team’s current cross-sectional analysis, for a total of 1,279 participants. The main variables considered in this study were age and body mass index (BMI), with researchers also assessing history of fractures as well as current and past use of calcium and vitamin D supplements. Serum vitamin D levels from 1,204 of the participants were also taken into account.
To test their novel hypothesis, researchers divided their 1,279 participants into three categories based on MHT use: 282 current users (22%), 380 past users (30%), and 617 never users (48%) and compared TBS among the groups. In addition to substantiating previous findings that MHT is associated with significantly higher BMD values at all sites, they also found that bone microarchitecture was better preserved among the current and past MHT users, as demonstrated by TBS, which also likely contributed to decreased risk of fracture.
Thus, MHT exerts a protective effect on both bone mass and structure. Interestingly, duration of MHT did not have an effect one way or the other on the results. However, the benefits on bone health did not dwindle with withdrawal from MHT; the increases in BMD values and TBS are seen for at least two more years, explains Papadakis. “What I think is most interesting about our large cohort study is the results of past users. The results of previous studies in this field have been quite contradictory regarding whether there is a very rapid rebound effect after the withdrawal of MHT. We were surprised to find that in past users, effects persist for at least two years after withdrawal,” he says.
Potential limitations of the study, titled “The Benefit of Menopausal Hormone Therapy on Bone Density and Microarchitecture Persists After its Withdrawal” and published in The Journal of Clinical Endocrinology & Metabolism, include reliance on participant self-reporting of MHT start date and discontinuation and what type of MHT they used, he adds. Moreover, researchers were not able to determine the amount of estrogen each participant took in. Additionally, this study was cross-sectional rather than randomized.
Clinical Implications: Double Duty
Regarding what the study offers to clinicians, Papadakis says, “I think the real question is if there is a place for MHT as an osteoporosis treatment. Maybe we start to think of MHT as a first-choice treatment for young postmenopausal women.” To be effective, researchers now believe that an antiosteoporotic agent should target both bone mass and bone microarchitecture, the latter being a shortcoming of current drug treatments. However, MHT does both, which may make it the more efficacious choice. In most postmenopausal women age 60 and younger, the benefits of using MHT outweigh the risks. In these women, MHT could be used to both prevent and treat osteoporosis for a period of around five to 10 years, and its effects will likely last for at least two years after treatment withdrawal.
Papadakis emphasizes that this new facet of MHT does not mean that it should be prescribed to all women or that it should be given indefinitely, despite that the bone health benefits it confers will dissipate. Rather, its role can be thought of as warding off bone fragility and potentially preserving quality of life for a subset of middle age women with no contraindications to MHT. Though temporary, these advantages could make a considerable difference in women’s lives. Furthermore, they would essentially treat two conditions with one form of therapy. “Other osteoporotic treatments can then be reserved for later in life,” Papadakis says. “Even when we stop the hormones, we do not need to introduce any immediate replacement treatment because, unlike other osteoporotic treatments, there is no rebound effect.”
Future research Papadakis and team would like to undertake includes exploring the association between estrogen and fat mass as well as the role of fat mass on bone health. “What we would like to do next in our cohort is to try to see if the effect on bone passes partly via an effect on fat tissue. Although we are in the very beginning stages of developing this hypothesis, people with excess abdominal fat are in a state of chronic inflammation and also present with an increased risk for fracture by a possibly related mechanism.”
- Horvath is a freelance writer based in Baltimore, Md. She wrote last month’s cover story on the on the effects of certain forms of contraception and endocrine-disrupting chemicals on vitamin D levels in the body.
- Age- and BMI-adjusted analysis showed higher TBS as well as BMD values at the lumbar spine, femoral neck, and total hip (primary endpoints) in current MHT users as compared to past and never users.
- Past MHT users demonstrated higher lumbar spine and total hip BMD and higher TBS than never users. Among past users, early discontinuers (<2 years) had significantly greater residual impact of MHT on TBS and BMD.
- Current and past MHT users had significantly lower 10-year loss of TBS and BMD at the lumbar spine and total hip than did never users.