Understanding Bone Health: A Comprehensive Guide to Osteoporosis, Current Treatments, and the Role of Hormone Replacement Therapy
Osteoporosis is a condition characterized by the loss of bone tissue and low bone density (1). These impairments cause bones to become weak and brittle, which significantly increases the risk for fractures (1). Bones remodel themselves by losing tissue through resorption and rebuilding tissue through formation (1,2). When bone tissue is lost faster than it can be rebuilt, bone mass is lost (1). What makes osteoporosis dangerous is that symptoms often do not present until a fracture has occurred (1). There are multiple factors that contribute to osteoporosis, but the main ones include advanced age and a decrease in sex hormones, particularly estrogen, which means that peri- and postmenopausal women are at highest risk for developing the condition (2,3). Due to the dangers of osteoporotic fracture and the frequency of the condition (roughly 10 million Americans have the condition), osteoporosis is an important health concern and has a variety of treatment options.
Current Treatments for Osteoporosis
While there is no cure for osteoporosis, there are pharmacological and nonpharmacological current treatments for Osteoporosis to help treat the condition. Nonpharmacological treatments include nutritional and lifestyle changes (such as increasing exercise and nutrient and vitamin intake) as well as increasing calcium intake (2). Pharmacological strategies include the use of bisphosphonates, which are agents that limit the process of bone resorption to strengthen bone architecture (2). There are different types of bisphosphonates available for treatment, which tests have shown can reduce bone fractures by 40-70 percent. (2). In the past, hormone replacement therapy (HRT), the process of replacing the estrogen that is naturally lost during menopause, has been used to help treat osteoporosis (2). However, recent studies have shown that HRT use can carry unfavorable risk-benefit ratios and should only be used for a specific group of patients (4).
The link between decreased estrogen levels and osteoporosis was first observed by Fuller Albright in 1941 (4). While HRT was originally prescribed as a treatment for menopause-associated symptoms, Albright’s observation eventually led to multiple observational studies suggesting that estrogen therapy helped prevent bone loss in peri- and postmenopausal women as well as improve cardiovascular health (4,5). As a result, estrogen (either alone or in combination with progesterone) became a widespread preventative treatment for osteoporosis (4). However, due to the publication of a study conducted by the Women’s Health Initiative (WHI) indicating unfavorable risk-benefit ratios, the use of HRT as a preventative measure for osteoporosis has become uncommon.
In the 1990s, the WHI was started with the interest in evaluating HRT’s effect on coronary heart disease and the incidence of breast cancer (6). Over 27,000 postmenopausal women ages 50 to 79 were enrolled in this study. Over 16,000 subjects with uteri were given either a combination of estrogen and progesterone (previous findings indicated that taking unopposed estrogen supplements were correlated with an increased risk for endometrial cancer) or placebo; over 10,000 participants without uteri were given either estrogen or placebo (6).
According to WHI publications, the group receiving the combination of estrogen and progesterone was observed to have an increase of breast cancer incidence and coronary heart disease with a decrease in osteoporotic fracture (5,6), which seemingly contradicted previous observational studies. This trial was then ended prematurely given that the findings suggested the risks of HRT outweigh any benefits (6). While these contradictory findings were surprising to researchers, when considering the fact that WHI participants had a mean age of 63 (much older than the average age of menopause onset), it is understandable since the observational studies focused on younger, symptomatic participants much closer to the age of menopause onset (5). This helped lead to the hypothesis that the effects and risks of HRT differed between age groups.
Possible Benefits of HRT
Before considering HRT, it is important to understand the benefits and risks of the treatment. Data from observational studies, the WHI trials, and additional studies found that HRT is correlated with roughly 34% reduction of fractures, both vertebral and nonvertebral (3,6). Because estrogen withdrawal is a major cause of weakened bone mass, using HRT reduces bone resorption which helps to prevent the loss of bone mass (6). HRT also alleviates menopause-associated symptoms. Women with significant symptoms are often directed to HRT as a primary treatment for menopause and generally only require a low dosage for a short amount of time (4).
Possible Risks of HRT
While HRT provides some benefits, it carries significant risks as well. The use of HRT is associated with slight increases in the risk of breast cancer, and that risk increases the longer HRT is used (4). This was confirmed by the WHI study, with participants using the combination of estrogen and progesterone having more developed tumors than participants receiving placebo (4,6). Endometrial cancer is an established risk of unopposed estrogen use, meaning that a combination of estrogen and progesterone must be prescribed for women who have not had hysterectomies (4). Because these risks are quite significant, the risk-benefit ratio and decision to use HRT as a preventative measure for osteoporosis is very individualized to the patient.
For women under 60 years of age (or less than 10 years since onset of menopause) with menopause-associated symptoms and a higher risk for fractures, the risk-benefit ratio of HRT as a treatment for menopause is generally favorable with the caveat that patients use a minimal dose for the shortest time (4). As a preventative measure for osteoporosis, the risk-benefit ratio is not favorable as a primary strategy (4). In order to maintain bone mass and density, a patient has to continue using HRT because bone density declines once treatment is stopped (3). This can be dangerous as many of the risks associated with HRT increase the longer the treatment is used. Because of this, the FDA does not recommend HRT as a primary preventative measure for osteoporosis (3). Additionally, little data exists to determine whether a lower dose of HRT has an effect on osteoporotic fracture incidence (3).
As a preventative measure for osteoporosis, recent data as well as the risk-benefit ratio does not support the use of HRT as a widespread treatment for the condition. While HRT can be considered in women within 10 years of menopause onset, women over 60 years of age with osteoporosis or a predisposition to it should use bisphosphonates as the first line treatment strategy. Should a patient want to use HRT as a primary treatment, any side effects and risks should be monitored by health professionals to ensure the safety of the patient.
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References
1. Sozen T, Ozisik L, Calik Basaran N. An overview and management of osteoporosis. European Journal of Rheumatology. 2017;4(1):46-56.
2. Tella SH, Gallagher JC. Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol. 2014 Jul;142:155-70.
3. Gambacciani M, Levancini M. Hormone replacement therapy and the prevention of postmenopausal osteoporosis. Prz Menopauzalny. 2014 Sep;13(4):213-20.
4. Compston JE. The risks and benefits of HRT. J Musculoskelet Neuronal Interact. 2004 Jun;4(2):187-90.
5. Chester RC, Kling JM, Manson JE. What the Women's Health Initiative has taught us about menopausal hormone therapy. Clin Cardiol. 2018 Feb;41(2):247-252.
6. Cagnacci A, Venier M. The Controversial History of Hormone Replacement Therapy. Medicina (Kaunas). 2019 Sep 18;55(9):602.