Osteoporosis — Medicine Library

Summary

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.

Definitions

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

Epidemiology

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.

Etiology

Primary osteoporosis (most common)

Type I (
postmenopausal osteoporosis): postmenopausal women [2][3]

Estrogen stimulates osteoblasts and inhibits osteoclasts.

The decreased estrogen levels following menopause lead to increased bone resorption.
Type II (senile osteoporosis): gradual loss of bone mass as patients age (especially > 70 years)
Idiopathic osteoporosis
- Idiopathic juvenile osteoporosis [4]
- Idiopathic osteoporosis in young adults [5]

Secondary osteoporosis

Drug-induced/
iatrogenic
- Most commonly due to systemic long-term therapy with corticosteroids (e.g., in patients with autoimmune disease) [3]
- Long-term therapy involving: [6]
  
  Anticonvulsants (e.g., phenytoin, carbamazepine)
  
  L-thyroxine
  
  Anticoagulants (e.g., heparin)
  
  Proton pump inhibitors
  
  Aromatase inhibitors (e.g., anastrozole, letrozole)
  
  Immunosuppressants (e.g., cyclosporine, tacrolimus)
  
  Androgen deprivation therapy (ADT)
Endocrine/metabolic: hypercortisolism, hypogonadism, hyperthyroidism, hyperparathyroidism, renal disease
Multiple myeloma

Additional risk factors [7]

Excessive alcohol consumption
Cigarette smoking
Immobilization or inadequate physical activity
Malabsorption (e.g., celiac disease), malnutrition (e.g., diet low in calcium and vitamin D), anorexia [8]
Low body weight
Family history of osteoporosis
Personal history of fracture

Clinical features

Mostly asymptomatic
Fragility fractures: pathological fractures that are caused by everyday-activities (e.g., bending over, sneezing) or minor trauma (e.g. falling from standing height) [9]

Common locations of major osteoporotic fractures: vertebral (most common) > femoral neck > distal radius (Colles fracture) > other long bones (e.g., humerus)

Vertebral compression fractures

Commonly asymptomatic but may cause acute back pain and possible point tenderness without neurological symptoms

Multiple fractures can lead to decreased height and thoracic kyphosis.

See “Vertebral fractures” for more information.

$Compression fractures of the vertebra$

Screening

Indications [10]

Screening is recommended in:
- Women ≥ 65 years of age
- Postmenopausal women < 65 years of age with ≥ 1 risk factor for osteoporosis
- 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:
- Younger men with risk factors for osteoporosis (e.g., long-term corticosteroid use; ADT for prostate cancer) [12][13]
- Men ≥ 70 years of age [7][12][14]

The majority of screening and prevention recommendations are for women; consult an endocrinologist for men with suspected osteoporosis.

Modality [10]

≥ 65 years of age: BMD assessment; DXA of lumbar spine and hips is preferred. [10][11][15]
< 65 years of age
- Stratify patients using an osteoporosis risk assessment tool, e.g., FRAX.
- For patients with a clinically significant risk of osteoporosis, obtain BMD assessment.

Further management

If the diagnostic criteria for osteoporosis are fulfilled, start treatment for osteoporosis.
For all other patients:
[16]
- Optimize bone health and discuss fall prevention.
- For high-risk individuals : Start pharmacotherapy for osteoporosis prevention. [11]
- Reassess
  BMD at regular intervals.
  
  There is a paucity of data on the value and optimal timing of repeating the BMD assessment.
  
  Determine the need for and frequency of screening intervals on an individual basis based on the initial BMD (T-score) and development of new risk factors for osteoporosis or fractures.

Suggested frequency of osteoporosis screening [16]
T-score (in SD)	Intervals
-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. [7][16]

Diagnosis

Approach [11]

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.
[11]
- T-score ≤ -2.5 standard deviations (SDs) on dual-energy x-ray absorptiometry (DXA)
- T-score -1 to -2.5 SD in patients at increased risk of major osteoporotic fracture
- History of a major osteoporotic fragility fracture (regardless of BMD)
Once confirmed:
- Consider screening all patients for common causes of secondary osteoporosis.
- Evaluate high-risk patients for vertebral fractures.
Consider bone turnover markers (BTMs) to assess fracture risk and monitor treatment response.

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

Bone mineral density (BMD) assessment [11][15]

Indications

Evaluation of suspected osteoporosis
Screening for osteoporosis in asymptomatic high-risk individuals

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][15]
Postmenopausal women and men > 50 years of age	BMD is calculated using the T-score. T-score ≤ -2.5 SD indicates osteoporosis [11][15] T-score -1 to -2.5 SD indicates osteopenia [11][15] T-score ≥ -1 SD is normal [11][15]
All other individuals	BMD is calculated using the Z-score. Z-score < -2 indicates BMD likely lower than expected for age [11][15]

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. [17]

DXA scan in osteopenia

Alternatives [15]

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: [15]
  
  Very tall or very short stature
  
  Significant degenerative disk disease
  
  BMI > 35 kg/m²
  
  Close monitoring of trabecular bone density changes (e.g., chronic glucocorticoid use, parathyroid hormone therapy)

Fracture risk assessment [11]

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 [11][14]

Laboratory studies [7][11]

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

Routine studies
- CBC, CMP, PTH, phosphate, and serum 25-hydroxyvitamin D
- 24-hour urine to measure calcium, creatinine, and sodium levels
Additional studies
- Evaluate for specific etiologies of secondary osteoporosis as guided by clinical assessment (e.g., celiac antibodies, TSH, myeloma screen).
- Consider BTMs to assess fracture risk and monitor treatment response. [11][18]
Findings
- Primary osteoporosis: Serum calcium, phosphate, and parathyroid hormone (PTH) levels are usually normal
- Secondary osteoporosis: See “Laboratory findings in common bone disorders” and/or relevant articles for details.

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][15][19][20]

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.

Indications
:
T-score ≤ -1.0 in individuals with one or more of the following [11][19]

Women ≥ 70 years of age or men ≥ 80 years of age

Height loss of ≥ 4 cm (> 1.5 inches)

Undocumented (self-reported) prior vertebral fracture

Kyphosis

Recent long-term glucocorticoid therapy
Modalities
[11]
[15]
- Vertebral fracture assessment (VFA): uses DXA to assess for vertebral fractures
- Lateral thoracic and lumbar spine x-ray
Supportive findings (on
x-ray)
- Increased radiolucency and cortical thinning [21]
- Vertebral compression fractures

Decreased bone density in osteoporosis $Thoracic wedge compression fracture$ Chronic lumbar compression deformity $Acute and chronic vertebral fractures$

Imaging for other skeletal fractures [11][22]

Indications
- Symptoms of fracture (e.g., pain, limited mobility)
- Thigh or groin pain in patients on long-term (∼ 5 years) bisphosphonate therapy [23]
Modalities
- First line: plain x-ray
- Second-line : Consider MRI or CT.
Supportive findings
- Radiographic signs of a fracture
- Atypical femoral fractures: Transverse noncomminuted fracture of the subtrochanteric region or shaft of the femur [24]
- Increased radiolucency (on x-ray/CT) and cortical thinning [21]

$Bisphosphonate-related atypical femoral fracture$ $Chalkstick fracture$

**DXA scan in osteopenia**
Dual-energy x-ray absorbtiometry (DXA) scan of a 59-year-old female patient
The T-scores are -1.6 for the lumbar spine (top image) and -0.5 for the femoral neck (bottom image). The graph indicates the T-score values for osteopenia (-1 to -2.5) and osteoporosis (≤ -2.5); since the lower T-score is used for diagnostic categorization, this patient meets the criteria for osteopenia. The three lines on the graph indicate the 90^th, 50^th, and 10^th percentile for bone density of the reference population over time.
BMD: bone mineral density
T-score: the difference in standard deviations between the patient's BMD and the BMD of a young adult female reference mean

Source: “Fig. 2, in: Comparison of QCT and DXA: Osteoporosis Detection Rates in Postmenopausal Women” by Na Li, Xin-min Li, Li Xu, Wei-jie Sun, Xiao-guang Cheng, Wei Tian, International Journal of Endocrinology, licensed under CC BY 3.0.

**Decreased bone density in osteoporosis**
X-ray lumbar spine (lateral view) of a patient with osteoporosis
The vertebrae have a low-density appearance as a result of the loss of trabecular bone, and the cortical outline (example indicated by white line) of each vertebra appears accentuated. Other findings that may be seen on a spine radiograph in osteoporosis include an accentuated trabecular pattern and biconcave or compressed vertebral configuration.

Source: “Fig. 1, in: Imaging Findings and Evaluation of Metabolic Bone Disease” by Anish A. Patel, Rohit Ramanathan, Joshua Kuban et al., Hindawi, licensed under CC BY 3.0. Modifications: Flipped the image to face left Deleted letter L. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Thoracic wedge compression fracture**
X-ray thoracic spine (lateral view) of a patient with osteoporosis
There is an insufficiency fracture of the T7 vertebral body, which is anteriorly wedged (green overlay) and accompanied by anterior subluxation (arrow) of the T6 vertebral body.
Wedge compression deformities are frequently osteoporotic, although alternatively may be pathologic (secondary to a focal bone lesion) or traumatic.
Red dashed outlines: normal vertebrae

Our great thanks to Dr. Kissig (Center for Diagnostic and Interventional Radiology, Hedwigshöhe, St. Hedwig, Berlin, and St. Josefs Hospital, Potsdam) for kindly providing this image.

**Chronic lumbar compression deformity**
X-ray lumbar spine (lateral view)
There is a chronic compression deformity (red dimension line) of the L4 vertebral body, with displacement (red overlay) toward the spinal canal beyond the posterior vertebral lines of L3 and L5 (white dotted line). Exuberant anterior osteophyte formation is visible at L3–4 (red dotted lines).

Source: © IMPP

**Acute and chronic vertebral fractures**
MRI lumbar spine (left: STIR image; right: T1-weighted; sagittal plane)
Compression deformities of the T8, T10, and L4 vertebrae (green overlays) are visible. The T8 and T10 fractures are hyperintense on the STIR image, indicating that they are recent. The compressed superior endplate of L4 is iso- to hypointense, indicating an old or chronic deformity. The hypointense appearance of the L2–3 intervertebral disc (green circle) on the STIR image indicates disc degeneration.

Source: © IMPP

**Bisphosphonate-related atypical femoral fracture**
X-ray right femur (AP view) of a patient with multiple myeloma treated with intravenous bisphosphonate therapy
An oblique fracture is seen in the subtrochanteric region of the right femur (indicated by arrows).
Atypical femoral fractures (AFFs; bisphosphonate-related proximal femoral fractures) are uncommon stress or insufficiency fractures, occurring in the femoral shaft.

Source: “Fig. 1b, in: Bilateral Atypical Femoral Fractures in a Patient with Multiple Myeloma Treated with Intravenous Bisphosphonate Therapy” by Ichiro Tonogai; Tomohiro Goto; Daisuke Hamada et al., Case Reports in Orthopedics, licensed under CC BY 4.0. Modifications: - cropped. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Chalkstick fracture**
© Massachusetts Medical Society. All rights reserved. AMBOSS SE, exclusive licensee.

Pathology

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

Differential diagnoses

Osteomalacia
Hyperparathyroidism
Metastases
Multiple myeloma
Intraosseous hemangioma

Thoracic vertebral hemangioma Intraosseous hemangioma in the lumbar vertebrae

The differential diagnoses listed here are not exhaustive.

**Intraosseous hemangioma in the lumbar vertebrae**
Standing X-ray of the lumbar spine: L2 shows hypertrophic sclerosis of the vertical trabeculae, which indicates an intraosseous hemangioma.

Source: © IMPP

Treatment

Approach [7][11]

All patients: Optimize bone health.
Older patients: Assess for and manage
risk factors for falls.
[7]
[25]
- Discuss fall prevention strategies.
- Identify and manage risk factors for falls using the CDC STEADI algorithm for falls.
- Recommend individual and/or group exercise interventions that incorporate strength and balance training.
- Refer to physical and/or occupational therapy as needed.
Start pharmacotherapy in the following situations:
- Diagnostic criteria for osteoporosis fulfilled
- Patients with osteopenia at increased risk of major osteoporotic fracture in the next 10 years
See also “Introduction to geriatrics” for general information on the prevention of falls in older individuals.

Pharmacotherapy for osteoporosis [11][26][27]

Indications [11]

Treatment: patients who fulfill any of the diagnostic criteria for osteoporosis
Prevention: patients with osteopenia and an increased probability of a major osteoporotic fracture in the next 10 years (as determined on a clinical risk assessment tool such as the FRAX)

General principles [11]

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
[12]
- Alendronate, risedronate, zoledronic acid, and teriparatide
- Denosumab is approved for men receiving ADT for prostate cancer.
Agents approved for glucocorticoid-induced osteoporosis
[7]
[11]
[28]

Bisphosphonates, denosumab, and teriparatide

Teriparatide may be more effective at preventing vertebral fractures in this patient group than the other agents.

Bisphosphonates for osteoporosis [7][11]

Indications: : preferred initial treatment in all patients [7][11][23][28]
Mechanism of action: inhibition of osteoclasts, which are involved in bone resorption
Agents:
The following are approved for both prevention and
treatment of osteoporosis.
- Alendronate [7][11]
- Risedronate [7][11]
- Ibandronate (only FDA-approved for postmenopausal women) [7][11]
- Zoledronic acid [7][11]
Adverse effects
[7]
[29]
- Osteonecrosis of the jaw
- Atypical femoral fractures
- Esophagitis
- Hypocalcemia
See also “Contraindications to bisphosphonate therapy” 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. [14]

Alendronate, risedronate, and zoledronic acid reduce hip, vertebral, and nonvertebral fracture risk; ibandronate reduces vertebral fracture risk only. [7]

Nonbisphosphonates [7][11][23]

General indications
- Alternative first-line agents in patients with contraindications to bisphosphonate therapy
- Second-line agents in those who do not improve with bisphosphonates or are unable to tolerate bisphosphonate therapy (e.g., due to adverse effects)
Specific indications: detailed below

Nonbisphosphonates for the treatment of osteoporosis [7][11][23]
	Specific indications [11][12]	Mechanism of action	Potential adverse effects
Denosumab [7][11]	Patients with impaired renal function Men undergoing ADT for prostate cancer	Monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL) Targets RANKL by mimicking osteoprotegerin → interference in osteoclast maturation → ↓ osteoclast activity [30]	Hypocalcemia Osteonecrosis of the jaw (uncommon)
PTH and PTH-related protein analogues Teriparatide [7] Abaloparatide [7]	Alternative for patients at high or very high risk of fracture Teriparatide: Treatment of glucocorticoid-induced osteoporosis [11][28]	Recombinant human parathyroid hormone that increases osteoblastic activity → increased bone growth [31][32]	Hypercalcemia (usually transitory) Dizziness, hypotension Tachycardia Muscle spasms Use with caution in patients with risk factors for osteosarcoma, e.g.: Paget disease of the bone (or unexplained elevation of alkaline phosphatase) Prior cancer or radiation therapy of the bone Open epiphyses
Romosozumab [33]	Alternative for postmenopausal women with multiple vertebral fractures or very high fracture risk	Monoclonal antibody against sclerostin Acts by increasing bone formation and reducing bone resorption	Avoid in patients at increased risk of cardiovascular disease, as romosozumab may increase the risk of: Myocardial infarction Stroke Cardiovascular death
Raloxifene [7]	Can be used in patients at increased risk of breast cancer [34]	Selective estrogen receptor modulator (SERM)	Increased risk of venous thromboembolism
Calcitonin [11]	Postmenopausal osteoporosis (rarely used because of the availability of more effective alternatives) [33] A short course may be prescribed for acute pain caused by vertebral fractures [35]	Inhibits bone resorption (monitor BMD) [36]	May increase overall cancer risk [7]
Hormonal therapy	Estrogen (women): not approved for osteoporosis treatment [23] Testosterone (men): used to treat low testosterone levels in men with hypogonadism [12]	Inhibits bone remodeling [37]	Estrogen therapy is associated with an increased risk of: Thromboembolism Stroke Myocardial infarction Certain cancers (e.g., breast, endometrial, ovarian)

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][23]

Mechanism of action: osteoporosis medication Regulation of calcium and phosphate metabolism

Monitoring and follow-up [11][14][23]

Regularly review patients to assess for problems with adherence; see “Managing chronic conditions.”
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 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	Insufficient data on optimal duration Consider discontinuing bisphosphonates after 5 years in women with no history of vertebral fractures. [7] In patients at very high risk of major osteoporotic fractures, consider a total duration of: 10 years for oral bisphosphonates 6 years for zoledronic acid in patients	Bisphosphonates can be discontinued temporarily (“bisphosphonate holiday”) after 3–5 years of treatment. Optimum duration of bisphosphonate holiday is unclear: Monitor BMD using DXA regularly and restart treatment if BMD declines or if the patient sustains a fracture.
Abaloparatide, teriparatide	2 years	Transition to bisphosphonates or denosumab after discontinuation.
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][14]

**Mechanism of action: osteoporosis medication**
– Calcitonin: inhibits osteoclast activity and reduces renal and gastrointestinal resorption of calcium
– Romosozumab: a monoclonal antibody that binds sclerostin, promoting bone formation and inhibiting bone resorption
– Selective estrogen receptor modulators (SERMs; e.g., raloxifene) and estrogens: suppress chemical mediators (e.g., cytokines, TGFb), resulting in inhibition of osteoclast bone resorption and promotion of osteoclast apoptosis
– Bisphosphonates (alendronate, risedronate): inhibit osteoclast activity and, therefore, bone resorption
– RANKL inhibitors (denosumab): bind to RANKL, preventing it from activating osteoclasts via the RANK receptor
– Strontium: activates osteoblasts and stimulates them to produce osteoprotegerin (OPG), which inhibits RANK-RANKL binding
– PTH/parathyroid analogs (teriparatide): promote both osteoblast and osteoclast activity but with the net result of increased bone mass
– Vitamin D: increases absorption of calcium and phosphate from the gastrointestinal tract

© AMBOSS

**Medication-related osteonecrosis of the jaw**
The underlying bone is exposed in a tooth gap, and the surrounding gums are inflamed, swollen, and erythematous.
These findings, together with a history of long-term therapy with antiresorptive medications (e.g., bisphosphonates or RANKL inhibitors), are highly suggestive of medication-related osteonecrosis of the jaw. Dental surgery and pressure points from dentures are common triggers for such lesions.

Source: “Stage 2 MRONJ” by Coronation Dental Specialty Group, Wikimedia Commons, licensed under CC BY-SA 4.0.

**Advanced medication-related osteonecrosis of the jaw**
Teeth of a 65-year-old patient 3 weeks after a tooth extraction; medication history included bisphosphonates and denosumab.
On the left mandible, a 2.5–3 cm area of the alveolar process surrounding the extraction site is completely exposed and appears necrotic.
In patients with a history of long-term therapy with antiresorptive medications (e.g., bisphosphonates or RANKL inhibitors such as denosumab), this appearance is highly suggestive of medication-related osteonecrosis of the jaw. Common triggers for such lesions include dental surgery and pressure points from dentures.

Source: “Fig. 2, in: Denosumab Related Osteonecrosis of the Jaw with Spontaneous Necrosis of the Soft Palate: Report of a Life Threatening Case” by Qaisi M, Hargett J, Loeb M, Brown J, Caloss R, Case Reports in Dentistry, licensed under CC BY 4.0.

**Regulation of calcium and phosphate metabolism**
When serum calcium levels decrease, parathyroid chief cells secrete parathyroid hormone (PTH), which regulates calcium levels via the following mechanisms:
1. PTH activates osteoclasts, which degrade bone, thereby releasing calcium and phosphate.
2. In the kidneys, PTH stimulates calcium reabsorption in the distal tubule and decreases phosphate reabsorption in the proximal tubule.
3. PTH increases the expression of 1α-hydroxylase in the kidneys, an enzyme required to synthesize calcitriol. Calcitriol, in turn, stimulates renal and intestinal reabsorption of both calcium and phosphate. In contrast to PTH, calcitriol promotes the mineralization of bone using calcium and phosphate.

© AMBOSS

Prevention

General measures [7][14]

Optimize
calcium and vitamin D intake.

Recommended daily intake of calcium: 1000–1200 mg [14]

Recommended daily intake of vitamin D: 800–1000 IU [14]
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” [38]

Pharmacotherapy for osteoporosis prevention [39]

Indication: individuals with osteopenia who are at high risk for osteoporotic fractures [11]
Preferred agents: bisphosphonates (see “Bisphosphonates for osteoporosis” for dosages) [11]
Alternatives for
postmenopausal women in whom
bisphosphonates are inappropriate
or who desire pharmacotherapy for management of menopause symptoms [11][40][41]

Raloxifene [11]

Consider estrogen or conjugated estrogen/bazedoxifene; see “Hormone replacement therapy” for dosages and details.

Related One-Minute Telegram

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External Resources

References

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