Osteoporosis is a skeletal condition in which the loss of bone mineral density (BMD) leads to decreased bone strength and increased susceptibility to fractures. Postmenopausal women and older adults are often affected, as an abrupt decrease in estrogen and age-related processes play a key role in the development of osteoporosis. Additional risk factors include physical inactivity, a diet low in calcium and vitamin D, smoking, and alcohol consumption. Osteoporosis usually remains asymptomatic until the first occurrence of a fragility fracture (typically following minor trauma). Patients may also present with thoracic hyperkyphosis and height loss secondary to multiple vertebral compression fractures. Diagnostic evaluation includes (e.g., ), fracture risk assessment, and workup for common causes of secondary osteoporosis. Fractures are usually confirmed through conventional x-ray. Pharmacotherapy is indicated in patients who fulfill the . Bisphosphonates, which inhibit bone resorption and can significantly decrease the risk of fractures, are the preferred first-line treatment. Nonbisphosphonates are indicated in patients who are unable to take bisphosphonates and those in whom bisphosphonate therapy has been unsuccessful. Prevention mainly comprises of adequate calcium and vitamin D intake and regular physical activity with strengthening exercises to maintain or even increase bone mass and improve balance, thereby reducing the risk of falls and fragility fractures. High-risk individuals should be offered and pharmacotherapy should be initiated in those with osteopenia at a high risk of fractures.
Primary osteoporosis (most common)
- Type I (postmenopausal osteoporosis): postmenopausal women 
- Type II (senile osteoporosis): gradual loss of bone mass as patients age (especially > 70 years)
- Idiopathic osteoporosis
- Most commonly due to systemic long-term therapy with corticosteroids (e.g., in patients with autoimmune disease) 
- Long-term therapy involving: 
- Endocrine/metabolic: hypercortisolism, hypogonadism, hyperthyroidism, hyperparathyroidism, renal disease
- Multiple myeloma
Additional risk factors 
- Mostly asymptomatic
Fragility fractures: that are caused by everyday-activities (e.g., bending over, sneezing) or minor trauma (e.g. falling from standing height) 
- Common locations of major osteoporotic fractures: vertebral (most common) > femoral neck > distal radius () > other long bones (e.g., humerus)
Osteoporosis is typically identified during screening in high-risk individuals (see “Screening for osteoporosis”).
- Assess BMD and estimate the risk of major osteoporotic fracture.
- The diagnosis is confirmed if any of the following diagnostic criteria for osteoporosis are fulfilled. 
- Consider screening all patients for common causes of .
- Evaluate high-risk patients for vertebral fractures.
- Consider BTMs) to assess fracture risk and monitor treatment response. (
Bone mineral density (BMD) assessment 
- Evaluation of suspected osteoporosis
- in asymptomatic high-risk individuals
Preferred modality: dual-energy x-ray absorptiometry
|BMD scores |
|Postmenopausal women and men > 50 years of age|
|All other individuals|
These studies are most commonly used when conventional DXA is unavailable.
- Peripheral DXA: measures BMD at the distal forearm
Quantitative computed tomography
- Provides a volumetric measurement of BMD at the lumbar spine and hip
- Can measure density of trabecular bone
- May be superior to DXA in patients with: 
Fracture risk assessment 
- Several calculators are used to estimate fracture risk during the diagnostic workup or screening for osteoporosis.
- FRAX (commonly used; see “Tips and Links”): estimates the 10-year probability of a major osteoporotic fracture 
Laboratory studies 
Consider screening all patients with newly diagnosed osteoporosis for common causes of secondary osteoporosis and potential contraindications for certain pharmacotherapy.
- Routine studies
- Additional studies
Screening for vertebral fractures 
- Indications: ≤ -1.0 in individuals with one or more of the following 
- Modalities 
- Supportive findings (on x-ray)
Imaging for other skeletal fractures 
- Supportive findings
The differential diagnoses listed here are not exhaustive.
- All patients: .
- Older patients: Assess for and manage risk factors for falls. 
- Start pharmacotherapy in the following situations:
- See also “Introduction to geriatrics” for general information on the prevention of falls in older individuals.
Pharmacotherapy for osteoporosis 
- Treatment: patients who fulfill any of the
- Prevention: patients with osteopenia and an increased probability of a in the next 10 years (as determined on a clinical risk assessment tool such as the FRAX)
General principles 
- Bisphosphonates are preferred first-line agents.
- Consider nonbisphosphonates as first-line alternatives in certain situations or as second-line agents if bisphosphonate therapy is unsuccessful or not tolerated.
- Combination therapy with agents of different classes is currently not recommended.
- Agents approved for osteoporosis treatment in men 
- Agents approved for glucocorticoid-induced osteoporosis 
Bisphosphonates for osteoporosis 
- Indications: preferred initial treatment in all patients 
- Mechanism of action: inhibition of osteoclasts, which are involved in bone resorption
- Agents: The following are approved for both prevention and treatment of osteoporosis.
- Adverse effects 
- See also “ ” and “Duration of pharmacotherapy for osteoporosis.”
Oral bisphosphonates should be taken in the morning with plenty of water at least 30 minutes before food and other medication, and the patient should maintain an upright position for at least 30 minutes after intake to prevent esophagitis. 
- General indications
- Specific indications: detailed below
|Nonbisphosphonates for the treatment of osteoporosis |
|Specific indications ||Mechanism of action||Potential adverse effects|
|Romosozumab || |
|Raloxifene || || |
|Calcitonin || || |
|Hormonal therapy|| |
Estrogen is not approved for the treatment of osteoporosis in women; if estrogen is prescribed to a patient with a uterus, it should always be combined with progesterone therapy to reduce the risk of endometrial hyperplasia. 
Monitoring and follow-up 
- Regularly review patients to assess for problems with adherence; see “Managing chronic conditions.”
- Consider BTMs to assess treatment efficacy and adherence. 
- Measure height yearly; if there is a ≥ 2 cm height loss, repeat imaging for vertebral fractures.
- Obtain DXA every 1–2 years for patients on treatment to monitor response. 
- Markers of improvement: stable or increasing BMD, no new fractures, normal or low BTMs
- If there is inadequate improvement : 
|Duration of pharmacotherapy for osteoporosis |
|Duration of therapy||Additional considerations|
|Abaloparatide, teriparatide|| |
|Denosumab|| || |
The benefits of nonbisphosphonates are lost rapidly after discontinuation; initiate another treatment for osteoporosis after cessation. 
- Optimize calcium and vitamin D intake.
- Treat vitamin D deficiency.
- Encourage physical activity, including strength (resistance) and balance training.
- Avoidance or minimization of the following:
- Tobacco use: See “Counseling on smoking cessation.”
- Excessive alcohol consumption: See “Counseling on alcohol abuse.”
- Glucocorticoid use; see also “Measures to prevent complications of steroid therapy” 
- Screening is recommended in:
- There is insufficient evidence to recommend routine screening for osteoporosis in men; consider screening:
Screening modality and further management 
- Modality: ; DXA of lumbar spine and hips is preferred 
- : Start fulfilled .
Diagnostic criteria not fulfilled 
- High-risk individuals
- Optimize bone health and discuss fall prevention.
- Start pharmacotherapy for osteoporosis prevention.
- Preferred: bisphosphonates (see “ ” for dosages) 
- Alternatives for postmenopausal women in whom bisphosphonates are inappropriate or who desire pharmacotherapy for management of menopause symptoms 
- Reassess BMD.
- High-risk individuals
|Suggested intervals for repeat BMD assessment |
|-2.0 to -2.4||within 3 years|
|-1.5 to -1.9||3–5 years|
|-1.0 to -1.4||5–10 years|
|> -1.0||> 10 years|