Estrogen’s role in bone health and its therapeutic potential in osteosarcopenia
Mandelli A, Tacconi E, Levinger I, et al. The role of estrogens in osteosarcopenia: from biology to potential dual therapeutic effects. Climacteric. 2021;1-7. doi: 10.1080/13697137.2021.1965118.
Osteosarcopenia is a particular term used to describe the coexistence of 2 pathologies, osteopenia/ osteoporosis and sarcopenia.14 Sarcopenia is characterized by a loss of muscle mass, strength, and performance. Numerous studies indicate that higher lean body mass is related to increased BMD and reduced fracture risk, especially in postmenopausal women.15
Menopause, muscle, and estrogen’s physiologic effects
Estrogens play a critical role in maintaining bone and muscle mass in women. Women experience a decline in musculoskeletal quantity and quality at the onset of menopause.16 Muscle mass and strength decrease rapidly after menopause, which suggests that degradation of muscle protein begins to exert a more significant effect due to a decrease in protein synthesis. Indeed, a reduced response to anabolic stimuli has been shown in postmenopausal women.17 Normalization of the protein synthesis response after restoring estrogen levels with estrogen therapy supports this hypothesis.18
In a meta-analysis to identify the role of estrogen therapy on muscle strength, the authors concluded that estrogens benefit muscle strength not by increasing the skeletal mass but by improving muscle quality and its ability to generate force.19 In addition, however, it has been demonstrated that exercise prevents and delays the onset of osteosarcopenia.20
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Estrogens play a crucial role in maintaining bone and skeletal muscle health in women. Estrogen therapy is an accepted treatment for osteoporosis, whereas its effects on sarcopenia, although promising, indicate that additional studies are required before it can be recommended solely for that purpose. Given the well-described benefits of exercise on muscle and bone health, postmenopausal women should be encouraged to engage in regular physical exercise as a preventive or disease-modifying treatment for osteosarcopenia.
Estrogens play a crucial role in maintaining bone and skeletal muscle health in women. Estrogen therapy is an accepted treatment for osteoporosis, whereas its effects on sarcopenia, although promising, indicate that additional studies are required before it can be recommended solely for that purpose. Given the well-described benefits of exercise on muscle and bone health, postmenopausal women should be encouraged to engage in regular physical exercise as a preventive or disease-modifying treatment for osteosarcopenia.
When should bone mass be measured in premenopausal women?
Conradie M, de Villiers T. Premenopausal osteoporosis. Climacteric. 2021:1-14. doi: 10.1080/13697137 .2021.1926974.
Most women’s clinicians are somewhat well acquainted with the increasing importance of preventing, diagnosing, and treating postmenopausal osteoporosis, which predisposes to fragility fracture and the morbidity and even mortality that brings. Increasingly, some younger women are asking for and receiving both bone mass measurements that may be inappropriately ordered and/or wrongly interpreted. Conradie and de Villiers provided an overview of premenopausal osteoporosis, containing important facts that all clinicians who care for women should be aware of.21
Indications for testing
BMD testing is only indicated in younger women in settings in which the result may influence management decisions, such as:
- a history of fragility fracture
- diseases associated with low bone mass, such as anorexia nervosa, hypogonadism, hyperparathyroidism, hyperthyroidism, celiac disease, irritable bowel disease, rheumatoid arthritis, lupus, renal disease, Marfan syndrome
- medications, such as glucocorticoids, aromatase inhibitors, premenopausal tamoxifen, excess thyroid hormone replacement, progesterone contraception
- excessive alcohol consumption, heavy smoking, vitamin D deficiency, calcium deficiency, occasionally veganism or vegetarianism.
BMD interpretation in premenopausal women does not use the T-scores developed for postmenopausal women in which standard deviations (SD) from the mean for a young reference population are employed. In that population, the normal range is up to -1.0 SD; osteopenia > -1.0 < -2.5 SD; and osteoporosis > -2.5 SD. Instead, in premenopausal patients, Z-scores, which compare the measured bone mass to an age- and gender-matched cohort, are employed. Z-scores > 2 SD below the matched population should be used rather than the T-scores that are already familiar to most clinicians.
Up to 90% of these premenopausal women with such skeletal fragility will display the secondary causes described above. ●
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Very specific indications are required to consider bone mass measurements in premenopausal women. When measurements are indicated, the values are evaluated by Z-scores that compare them to those of matched-aged women and not by T-scores meant for postmenopausal women. When fragility or low-trauma fractures or Z-scores more than 2 SD below their peers are present, secondary causes of premenopausal osteoporosis include a variety of disease states, medications, and lifestyle situations. When such factors are present, many general women’s health clinicians may want to refer patients for consultation to a metabolic bone specialist for workup and management.
Very specific indications are required to consider bone mass measurements in premenopausal women. When measurements are indicated, the values are evaluated by Z-scores that compare them to those of matched-aged women and not by T-scores meant for postmenopausal women. When fragility or low-trauma fractures or Z-scores more than 2 SD below their peers are present, secondary causes of premenopausal osteoporosis include a variety of disease states, medications, and lifestyle situations. When such factors are present, many general women’s health clinicians may want to refer patients for consultation to a metabolic bone specialist for workup and management.