Osteoporosis

Last updated: July 6, 2022

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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 BMD assessment (e.g., dual-energy x-ray absorptiometry), 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 diagnostic criteria for osteoporosis. 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 screening for osteoporosis and pharmacotherapy should be initiated in those with osteopenia at a high risk of fractures.

  • Osteoporosis: loss of trabecular and cortical bone mass which leads to bone weakness and increased susceptibility to fractures
  • Osteopenia: decreased bone strength but less severe than osteoporosis
  • Sex: > (∼ 4:1)
  • Age of onset: 50–70 years
  • Demographics: higher incidence in individuals of Asian, Hispanic, and northern European ancestry [1]

Epidemiological data refers to the US, unless otherwise specified.

Primary osteoporosis (most common)

Secondary osteoporosis

Additional risk factors [8]

Approach [11]

Osteoporosis is typically identified during screening high-risk individuals (see “Prevention”).

Osteoporosis is diagnosed in patients with a T-score ≤ -2.5 SD and/or a fragility fracture. [11]

Bone mineral density (BMD) assessment [11][12]

Indications

Preferred modality: dual-energy x-ray absorptiometry

DXA measures BMD; at the lumbar spine and hip/femoral neck using two x-ray beams. Findings are represented in terms of BMD scores that compare results to a reference population.

BMD scores [11][12]
Postmenopausal women and men > 50 years of age
  • BMD is calculated using the T-score.
  • T-score ≤ -2.5 SD indicates osteoporosis [11][12]
  • T-score -1 to -2.5 SD indicates osteopenia [11][12]
  • T-score ≥ -1 SD is normal [11][12]
All other individuals
  • BMD is calculated using the Z-score.
  • Z-score < -2 indicates BMD likely lower than expected for age [11][12]

DXA evaluates bone quantity. The trabecular bone score uses data from DXA images to evaluate bone quality and may sometimes be used to further stratify fracture risk. [13]

Alternatives [12][14]

These studies are most commonly used when conventional DXA is unavailable.

Fracture risk assessment [11]

Laboratory studies [8][11]

Consider screening all patients with newly diagnosed osteoporosis for common causes of secondary osteoporosis and potential contraindications for certain pharmacotherapy.

Treat vitamin D deficiency and ensure at least 2 weeks of recommended daily intake of calcium before obtaining 24-hour urine calcium. [11]

Screening for vertebral fractures [11][12][17][18]

Vertebral fractures are common in patients with osteoporosis, asymptomatic in up to two-thirds of cases, and associated with a high risk of future fractures.

Imaging for other skeletal fractures [11][20]

  • Thin, disconnected trabecular structures
  • Attenuated, pitted cortical bone
  • Increased osteoclast number and activity

The differential diagnoses listed here are not exhaustive.

Approach [8][11]

Optimize bone health [8][15]

Discuss fall prevention [8][24]

  • Discuss fall prevention strategies in all older patients.
  • Identify and manage risk factors for falls.
    • Risk factors include a history of falls and the presence of gait and balance issues.
    • Consider multifactorial interventions as needed.
  • Recommend individual and/or group exercise interventions that incorporate strength and balance training.
  • Refer to physical and/or occupational therapy as needed.

Pharmacotherapy for osteoporosis

Indications [11]

General principles [11]

Bisphosphonates for osteoporosis [8][11]

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. [15]

Alendronate, risedronate, and zoledronic acid reduce hip, vertebral, and nonvertebral fracture risk; ibandronate reduces vertebral fracture risk only. [8]

Nonbisphosphonates [8][11][21]

Nonbisphosphonates for the treatment of osteoporosis [8][11][21]
Specific indications [11][25] Mechanism of action Potential adverse effects
Denosumab [8][11]

PTH and PTH-related protein analogue

  • Teriparatide [8]
  • Abaloparatide [8]
Romosozumab [31]
  • Monoclonal antibody against sclerostin
  • Acts by increasing bone formation and reducing bone resorption
Raloxifene [8]
  • Can be used in patients at increased risk of breast cancer [32]
Calcitonin [11]
  • Inhibits bone resorption (monitor BMD) [34]
  • May increase overall cancer risk [8]
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. [11][21]

Monitoring and follow-up [11][15][21]

  • Regularly review patients to assess for problems with adherence.
  • Consider BTMs to assess treatment efficacy and adherence. [11]
  • 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. [11]
  • Markers Indicators of improvement: stable or increasing BMD, no new fractures, normal or low BTMs
  • If there is inadequate improvement : [11]
    • Consider alternative agents or reevaluate for secondary osteoporosis.
    • Consider referral to a clinical endocrinologist or osteoporosis specialist, if available.
Duration of pharmacotherapy for osteoporosis [11]
Duration of therapy Additional considerations
Bisphosphonates
Abaloparatide, teriparatide
  • 2 years
Romosozumab
  • 1 year
Denosumab
  • Indefinite
  • Transition to another antiresorptive agent.

The benefits of nonbisphosphonates are lost rapidly after discontinuation; initiate another treatment for osteoporosis after cessation. [11][15]

Screening for osteoporosis

Indications

Screening recommendations vary. The following recommendations are mainly consistent with the 2018 US Preventive Services Task Force (USPSTF). [14]

  • Screening is recommended in:
    • Women ≥ 65 years of age
    • Women < 65 years of age at increased risk of osteoporosis as determined by a clinical risk assessment tool (e.g., osteoporosis risk assessment instrument, osteoporosis self-assessment tool, FRAX)
    • Individuals with a history of low-trauma fracture after 50 years of age [11]
  • There is insufficient evidence to recommend routine screening for osteoporosis in men; consider screening:

Screening modality and further management [14]

T-score
(in SD)

Suggested intervals for repeat BMD assessment [37]
-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

Short-interval (within 2–3 years) reassessment of BMD in individuals who do not fulfill the diagnostic criteria for osteoporosis is not routinely recommended. [8][37]

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