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Menopausal Bone Loss: Timing is Everything

Osteoporosis is a chronic, progressive, and incurable disease requiring lifelong intervention. A study conducted in 2013-2014 revealed that 6.8% of women aged 50-59 already had osteoporosis, and 34.9% were diagnosed with osteoporosis by the age of 80. Although the impact of osteoporosis manifests in the form of fractures during older age, the most significant bone loss occurs during the menopause transition. Recognizing and addressing this menopausal transition bone loss is crucial to long-term bone health and reduced mortality risk.


Osteoporosis contributes to over two million fractures in the US annually, leading to more than 500,000 hospital admissions. The risk of a white woman in America experiencing an osteoporotic fracture in her lifetime exceeds 40%, with hip fractures being particularly problematic due to a higher disability rate than all other types of fractures combined. Shockingly, hip fractures elevate the likelihood of death by 25% within one year of the incident.


Bone density peaks in women around age 30. Bone turnover remains relatively consistent until the the onset of peri-menopause, when decreased estrogen levels lead to faster bone resorption than formation. From 1-3 years before menopause until 5-10 years after, women undergo rapid bone mass reduction, about 2% per year, resulting in a total loss of 10-12% in their hips and spine. After this period, the rate of bone loss drops to 0.5% per year, but the imbalance persists, culminating in an average 30% total bone loss by age 80.


Although age-related bone loss is normal, significant density loss, measured by dual-energy X-ray absorptiometry (DXA) or indicated by fractures, requires medical attention. Risk factors for osteoporosis include age, weight under 127 lbs, family history, and smoking. Some diseases, certain drugs, and some surgeries also can increase risk. Menopausal women with specific risk factors, particularly a history of fractures after menopause, should have their bone density checked via DXA. Additionally, women over 70 years old experiencing height loss should undergo spine imaging.


Women with DXA scores indicating low bone density should receive additional testing to rule out other causes of bone loss besides osteoporosis. Your doctor may order blood tests like complete blood cell count (CBC) and a basic metabolic panel. Additionally, a 24-hour check of urinary calcium may identify women with low (or high) calcium absorption. Tests for vitamin D deficiency, GI issues, thyroid disorders, bone cancers, and other conditions also are not uncommon.


To maintain bone health, women should ensure adequate vitamin D and calcium intake, exercise regularly, adopt a healthy diet, and avoid smoking and excessive alcohol consumption. Women over 50 should target 600 IU of vitamin D (800 IU for those over 70) and 1200 mg of calcium daily. Although obtaining these nutrients through food and sunlight exposure (in the case of vitamin D) is preferable, supplementation may be necessary; however, excessive calcium supplementation (beyond 1200 mg) increases the risk of kidney stones. Note that despite these measures reducing osteoporosis risk, they will not counter the accelerated bone loss during menopause or increase post-menopausal bone density.


Women who enter menopause with bone density scores on the low end of normal should talk with their doctor about the pros and cons of preventative drug therapy. Osteoporosis prevention drugs work by inhibiting bone resorption (MHT, Duavee, bisphosponates) or promoting bone formation (raloxifene). Menopausal hormone therapy (MHT) is effective in reducing bone loss during menopause and is recommended by The Menopause Society as the preferred treatment for the prevention of osteoporosis. Duavee is the tradename for a drug containing bazedoxifene, a selective estrogen receptor modulator (SERM), and conjugated estrogens. It significantly prevents bone loss, and, since bazedoxifene acts as an estrogen antagonist in the uterus, menopausal women do not need to add a progestogen to protect their uterus while they are taking it. Another type of osteoporosis prevention drugs called bisphosphonates work by impairing the cells that break down bone, thereby increasing bone density. Bisphosphonates are typically considered for women who cannot or wish not to take estrogen or who have stopped estrogen therapy. Finally, raloxifene, which acts as a SERM, increases bone density in menopausal women but can have side effects. Premenopausal women should not take raloxifene since it decreases their bone density. Raloxifene is prescribed for menopausal women with high risk of breast cancer or who have had breast cancer but have few hot flashes. Unfortunately, the preventative effects end once these drugs are discontinued. For example, the beneficial effects of MHT on bone loss are completely reversed within 2 years of stopping therapy.


For diagnosed osteoporosis, treatment aims to reduce fracture risk, with options like raloxifene or bisphosphonates for moderate risk and bisphosphonates or denosumab for higher risk. Raloxifene reduces fracture risk in women with osteoporosis by as much as 50%. Raloxifene is an option for menopausal women with a low risk of hip fracture, an increased risk of breast cancer, and low risk of stroke and blood clots. Bisphosphonates, like alendronate, risedronate, ibandronate, and zoledronate, reduce the risk of fractures by 70% in menopausal women with osteoporosis, but women who take bisphosphonates may need to take drug "holidays" since bisphosphonate use increases the risk of atypical fracture after 3 years. Women with a higher fracture risk should be cycled off bisphosphonates and onto a different osteoporosis treatment drug instead of taking the drug holiday. Denosumab is a monoclonal antibody that inhibits a molecule that stimulates bone resorption, thereby increasing bone density. It reduces fracture risk as much as 68% and increases bone density in 10 years by more than 20%. The positive effects of denosumab disappear soon after therapy ceases so "holidays" are not appropriate.


For women at high to imminent risk of fracture, so-called osteoanabolic (bone-building) drugs are appropriate because they more effective at increasing bone density and reducing fracture risk. Unfortunately, however, their ability to stimulate bone growth only lasts for 1-2 years. Additionally, they are only available by injection, and they have significant side effects. For example, parathyroid receptor agonists like teriparatide and abaloparatide can cause high calcium levels, dizziness when changing positions, and possibly bone tumors. Romosozumab, a monoclonal antibody, is not recommended for women at high risk of cardiovascular disease or who have had heart attacks or strokes.


In summary, peri-menopausal and menopausal women should adopt lifestyle measures to reduce risk factors for osteoporosis, and women over 50 should talk with their doctors about preventative screening. Medical intervention, tailored to individual risk and health conditions, can effectively limit bone loss, but osteoporosis prevention drugs must be taken indefinitely to sustain their effects. Women diagnosed with osteoporosis need appropriate treatment to reduce their fracture risk since hip and spine fractures are closely linked with increased mortality.



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