Postmenopausal osteoporosis is a common condition caused by estrogen deficiency after menopause, leading to fragile bones and an increased risk of fractures. About half of all postmenopausal women will experience a fragility fracture (a fracture from minimal trauma), and the costs in the United States already exceed $57 billion per year. This patient-focused article explains how osteoporosis is diagnosed and evaluated, reviews the lifestyle changes and medications that can prevent fractures, and clarifies how doctors decide who needs treatment—especially women at “very high risk.” It is based on a comprehensive clinical practice review published in the New England Journal of Medicine.
The clinical problem starts with a common scenario: a 69-year-old woman has just received her first bone density scan (called dual-energy x-ray absorptiometry, or DXA). Her T scores are −2.6 at the lumbar spine and −2.3 at the total hip. She fell while walking 18 months ago and fractured her left humerus (upper arm bone). Imaging of her spine, performed because she lost 5 cm (2 inches) of height and developed moderate thoracic kyphosis (a forward curvature of the upper back), shows two vertebral compression fractures. How should this patient be evaluated and treated?
Postmenopausal osteoporosis is caused by estrogen deficiency after menopause. Low estrogen levels increase the activity of osteoclasts (cells that break down bone) and speed up bone resorption—the process of removing bone tissue—so that bone loss outpaces bone formation. This is especially rapid in the years immediately before and after menopause. The result is low bone mineral density, deteriorated bone microarchitecture, decreased bone strength, and a higher risk of fragility fractures.
Fragility fractures are defined as those occurring with no associated trauma, or with trauma equivalent to falling from a standing height or less. These fractures are extremely common and cause pain, disability, and reduced quality of life. After a hip fracture, many women never regain independence. In fact, 20% are institutionalized, and the risk of death within 1 year doubles. Non-White women who have hip fractures are more likely to die within 6 months, less likely to regain independence, and receive less timely surgery and rehabilitation than White women. The annual health care cost associated with postmenopausal osteoporosis fractures in the United States is currently $57 billion, and this is projected to exceed $95 billion by 2040.
Osteoporosis is asymptomatic until the first clinical fracture. The gold standard for identifying patients at risk is bone mineral density measurement with DXA. Each standard deviation (SD) reduction below a T score of 0 is associated with a doubling or tripling in the risk of fracture.
Most guidelines recommend DXA of the spine and hip for postmenopausal women 65 years of age or older, and for postmenopausal women younger than 65 who have risk factors. Forearm bone mineral density can also predict fracture, and may be measured when the recommended sites are not evaluable, or when hyperparathyroidism is present.
Osteoporosis is formally diagnosed when either of the following is present:
In the United States, approximately 20% of women over 50 and 30% of women 65 or older meet DXA criteria for osteoporosis. Osteoporosis is more common among White, Asian, and Hispanic women than among non-Hispanic Black women. An additional 40% of postmenopausal women have low bone mass (osteopenia, defined as a T score between −1.0 and −2.49).
Fragility fractures of the spine, hip, forearm, humerus, and pelvis are diagnostic of osteoporosis even when T scores are higher than −2.5. The occurrence of a fragility fracture is associated with a marked increase in the imminent risk of additional fractures. Vertebral compression fractures are the most common osteoporotic fractures; they are frequently painful and cause height loss, but they may be asymptomatic. Vertebral fractures are associated with increased mortality, and their presence influences diagnosis, risk stratification, and treatment decisions.
Several clinical risk factors increase a woman’s chance of having osteoporosis or a fracture. According to the article, the key risk factors include:
The evaluation of a woman with suspected or confirmed postmenopausal osteoporosis starts with a thorough history focusing on previous fractures and risk factors. A physical examination should look for kyphosis and height loss. If height loss is greater than 1.5 inches (3.8 cm) or other signs suggest vertebral fracture, the doctor should order spine imaging—either vertebral fracture analysis (a low-radiation image obtained on a densitometer) or standard spine radiography.
Fracture risk can be estimated using the fracture risk assessment tool (FRAX) or other validated calculators. FRAX estimates the 10-year probability of a major osteoporotic fracture and of a hip fracture, based on clinical risk factors, with or without bone mineral density measurement. Many experts consider a hip fracture risk of ≥3% or a major osteoporotic fracture risk of ≥20% to be high enough to treat, even if the T score is above −2.5.
Another tool is the trabecular bone score (TBS), an FDA-cleared, Medicare-covered measure obtained from a DXA image using additional software. TBS is an indirect measurement of spine trabecular microarchitecture (the internal structure of bone), and it predicts fracture risk independent of bone mineral density. It can be used to adjust FRAX scores and is most useful when it influences treatment decisions—for example, in women with osteopenia or when fracture risk is close to an intervention threshold. TBS should not be used alone to diagnose osteoporosis.
Newer FDA-approved software also allows “opportunistic screening” from routine clinical CT scans to measure volumetric bone mineral density, bone strength, and prevalent vertebral fractures. Evidence suggests this technology performs at least as well as DXA. High-resolution peripheral quantitative CT (HRpQCT) can also measure bone microstructure and strength and predicts fracture risk independently, but it is not FDA-approved for diagnosis.
The article also emphasizes that laboratory evaluation is necessary. At minimum, doctors should measure serum creatinine, calcium, albumin, 25-hydroxyvitamin D, alkaline phosphatase, phosphate, and a complete blood count (CBC) to exclude contraindications to medications. Other tests may be appropriate depending on the situation, including parathyroid hormone (PTH), serum or urine protein electrophoresis (SPEP/UPEP), thyroid-stimulating hormone (TSH), erythrocyte sedimentation rate (ESR), celiac disease testing (transglutaminase IgA antibody and IgA level), and 24-hour urine calcium. These tests help identify alternative diagnoses such as osteomalacia, primary hyperparathyroidism, cancer, myeloma, chronic kidney disease–mineral and bone disorder, and other metabolic bone diseases.
The fundamental goal of treatment is to prevent fractures—either before the first fracture (primary prevention) or before a subsequent fracture (secondary prevention). Lifestyle modifications apply to all women with postmenopausal osteoporosis. Patients should be encouraged to:
Most guidelines recommend 1000 to 1200 mg of calcium daily, preferably from diet, and 400 to 1000 IU of vitamin D daily. Some experts suggest adjusting vitamin D intake to achieve serum 25-hydroxyvitamin D levels above 20 to 30 ng per milliliter, although this approach is controversial and not supported by rigorous data.
The evidence for calcium and vitamin D supplementation in reducing fractures is debated. Limited evidence suggests that supplemental calcium combined with vitamin D significantly reduces hip fractures, but not nonvertebral or vertebral fractures, in patients with postmenopausal osteoporosis. Still, because most osteoporosis medications were studied together with calcium and vitamin D, and some medications can cause low blood calcium (hypocalcemia), adequate intake is prudent. Potential risks of calcium supplements include kidney stones (nephrolithiasis) and, according to some meta-analyses, an increased incidence of cardiovascular events—although the studies in those meta-analyses were not designed to assess cardiovascular outcomes.
Pharmacologic therapies for postmenopausal osteoporosis work by either reducing bone resorption (antiresorptive medications) or stimulating bone formation (anabolic medications). All approved medications reduce vertebral fracture risk, and some also reduce nonvertebral and hip fracture risk. The choice of therapy must consider osteoporosis severity, fracture risk, coexisting conditions, and patient preferences and contraindications.
For women at high risk of fracture, most guidelines recommend bisphosphonates as initial treatment because of their efficacy, safety, convenience, low cost, and lasting effects after stopping. Four oral and intravenous bisphosphonates are FDA-approved for postmenopausal osteoporosis:
Oral bisphosphonates are poorly absorbed and can irritate the upper gastrointestinal tract. Intravenous zoledronate is preferred for patients with gastrointestinal side effects or esophageal dysfunction. Acute-phase reactions (fever, muscle aches) may occur with zoledronate but can be reduced with hydration and acetaminophen before and after the infusion.
Long-term bisphosphonate use has been associated with rare complications: osteonecrosis of the jaw (an area of exposed bone in the jaw that does not heal within 8 weeks) and atypical femur fractures (low-trauma fractures in the thigh bone with specific x-ray patterns). In patients taking standard doses for postmenopausal osteoporosis, these risks are estimated to be very low.
Denosumab is a human monoclonal antibody that binds to RANK ligand (RANKL), inhibiting osteoclast formation, function, and survival. It is given as 60 mg subcutaneously every 6 months. In 3-year randomized controlled trials, denosumab lowered the risk of spine, hip, and nonvertebral fractures compared with placebo, with reductions of 68% for vertebral, 40% for hip, and 20% for nonvertebral fractures. In long-term, open-label extension studies, the lower fracture risk was maintained.
Although gains in bone mineral density are greater with denosumab than with bisphosphonates, evidence for a greater reduction in fracture risk is limited. Rare side effects include osteonecrosis of the jaw, atypical femur fracture, and hypocalcemia—particularly in patients with advanced chronic kidney disease (stage 4 or 5) or vitamin D deficiency. It is important to note that stopping denosumab can cause rebound bone loss and an increased risk of fractures, so patients should not discontinue it without discussing a transition to another treatment with their doctor.
Conjugated equine estrogen (CEE, 0.625 mg daily orally) decreases bone resorption. In trials, it reduced vertebral fractures by 34%, hip by 29%, and nonvertebral by 21%. However, estrogen therapy carries significant risks: when used alone, it can increase the risk of stroke; when combined with medroxyprogesterone, it increases risks of venous thromboembolism (blood clots), stroke, coronary heart disease, breast cancer, dementia, and thromboembolic events. It is contraindicated in women with a history of breast cancer, coronary heart disease, active liver disease, unexplained vaginal bleeding, or increased risk of endometrial cancer.
Raloxifene (60 mg daily orally) is a SERM that has weak estrogen agonist activity in bone and decreases osteoclastic bone resorption. It reduces vertebral fractures by 40%, but has not been shown to reduce hip or nonvertebral fractures. Side effects include venous thromboembolism (VTE), hot flashes, night sweats, peripheral edema, leg cramps, and an increased risk of death from stroke. It is contraindicated in women with a history of VTE, pulmonary embolism, or retinal vein thrombosis.
Anabolic agents stimulate bone formation and are generally reserved for women at very high risk of fracture. Two FDA-approved medications are:
Anabolic agents are contraindicated in women with bone metastases, skeletal cancers, a history of skeletal radiation, increased risk of osteosarcoma (a rare bone cancer), Paget’s disease, hypercalcemic disorders, unexplained elevated alkaline phosphatase, or hypersensitivity to the medication.
Doctors categorize patients with osteoporosis into “high risk” or “very high risk” to guide treatment selection. “High risk” is typically defined as meeting minimal intervention thresholds—for example, a T score of −2.5 or lower, a fragility fracture, or a FRAX 10-year risk of hip fracture ≥3% or major osteoporotic fracture ≥20%. “Very high risk” is typically defined as:
Because anabolic agents (teriparatide or abaloparatide) stimulate new bone formation and have the greatest fracture-risk-reduction effects, most guidelines recommend anabolic agents as the initial treatment for women at very high risk, unless there are contraindications. For women at high risk (but not very high risk), bisphosphonates are typically the first choice. Denosumab is also an antiresorptive option and may be considered in certain circumstances, such as when oral bisphosphonates are not tolerated or in women with chronic kidney disease (after careful evaluation).
Returning to the case of the 69-year-old woman in the opening vignette: she has two vertebral fractures, a T score of −2.6 at the spine, and a prior humerus fracture from a fall. She meets the criteria for very high risk because of multiple vertebral fractures, even though her T score is not below −3.0. According to the authors’ recommendations, this patient should be started on an anabolic agent (teriparatide or abaloparatide) to reduce her imminent risk of subsequent fractures.
This clinical practice review acknowledges several areas of uncertainty. First, intervention thresholds vary among different guidelines; for example, some suggest treating women with FRAX-estimated high risk even without a low T score, but the evidence supporting treatment based purely on FRAX is less robust than evidence based on T scores or existing fractures. Second, whether calcium and vitamin D supplementation actually reduces fractures remains debated—limited evidence shows a reduction in hip fractures, but not in nonvertebral or vertebral fractures. Third, some meta-analyses suggest a possible increase in cardiovascular events with calcium supplements, but those studies were not designed to assess cardiovascular outcomes. Fourth, the optimal duration of therapy and the best sequence of treatments (antiresorptive after anabolic, or vice versa) are not fully defined. Finally, although very low, the risks of rare complications such as osteonecrosis of the jaw and atypical femur fractures with long-term antiresorptive use should be shared with patients.
If you are a postmenopausal woman, talk to your doctor about your risk factors for osteoporosis and whether you need a DXA scan. The following steps can help protect your bones and prevent fractures:
The article emphasizes that osteoporosis is treatable and that effective options exist to significantly reduce fracture risk. No single treatment works for everyone, so the choice of medication should be made together with your doctor, taking into account your fracture risk, other medical conditions, and personal preferences.
Postmenopausal osteoporosis is a condition caused by estrogen deficiency after menopause. Low estrogen increases bone breakdown, leading to low bone density, weakened bone structure, and higher fracture risk. About half of all postmenopausal women will experience a fragility fracture, which occurs from minimal trauma, such as falling from standing height.
Osteoporosis is diagnosed if you have a fragility fracture, especially of the spine, hip, wrist, humerus, or pelvis, even if your bone density T score is above -2.5. It is also diagnosed if a DXA scan shows a T score of -2.5 or lower at the lumbar spine, total hip, or femoral neck.
Most guidelines recommend DXA bone density testing for postmenopausal women age 65 or older. Testing is also recommended for younger postmenopausal women who have risk factors, such as previous fracture, parental hip fracture, low body weight, smoking, or use of medications like glucocorticoids.
Lifestyle changes include stopping smoking, limiting alcohol, doing weight-bearing exercise, and preventing falls. Most guidelines recommend 1000 to 1200 mg of calcium daily, preferably from diet, and 400 to 1000 IU of vitamin D daily. Getting enough calcium and vitamin D is especially important when taking osteoporosis medications.
Medication options include bisphosphonates (like alendronate and zoledronic acid), denosumab, estrogen therapy, raloxifene, and anabolic agents (teriparatide and abaloparatide). All approved medications reduce vertebral fracture risk, and some also reduce hip and nonvertebral fracture risk. Your doctor chooses based on your fracture risk and medical conditions.
Anabolic agents, such as teriparatide or abaloparatide, are generally recommended as initial treatment for women at very high risk of fracture. Very high risk includes a T score below -3.0, a fragility fracture with a T score of -2.5 or lower, or multiple vertebral fractures. These medications stimulate new bone formation.
This patient-friendly article is based on peer-reviewed research published in the New England Journal of Medicine:
Note: This article is intended for educational purposes and does not replace professional medical advice. Always consult your healthcare provider for personal medical decisions.
Use collapsible tabs for more detailed information that will help customers make a purchasing decision.
Ex: Shipping and return policies, size guides, and other common questions.