- ACRONYMS AND DEFINITIONS
- ACP - American College of Physicians
- ACR - American College of Rheumatology
- AACE - American Association of Clinical Endocrinologists
- BMD - Bone mineral density
- DXA - Dual-energy x-ray absorptiometry
- FRAX - Fracture risk assessment tool
- GC - Glucocorticoids
- IOF - International Osteoporosis Foundation
- NAM - National Academy of Medicine
- USPSTF - U.S. Preventive Services Task Force
- VTE - Venous thromboembolism
- PATHOPHYSIOLOGY
- Overview
- Osteoporosis is a bone disorder marked by decreased bone strength and an increased risk of fracture
- Osteoporosis generally occurs because of an imbalance in bone remodeling
- Mature adult bones continually undergo a process of bone remodeling where old bone is replaced with new bone
- Bone remodeling is governed by two types of cells:
- Osteoblasts - cells that produce new bone
- Osteoclasts - cells that resorb old bone
- Osteoblast and osteoclast activity is modulated by a number of hormones and cytokines. Imbalances in these modulators can lead to inefficient remodeling, excessive osteoclast activity, and eventually, osteoporosis.
- A protein called receptor activator of nuclear factor-κβ ligand (RANKL) has been found to play a pivotal role in stimulating osteoclast activity. RANKL production is increased by the hormonal changes seen in menopause. It is inhibited by a protein called osteoprotegerin (OPG). The osteoporosis drug denosumab binds RANKL and inactivates it.
- Other hormones and cytokines play a role in bone remodeling, and in many cases, their specific role has not been fully elucidated [1]

- RISK FACTORS
- Overview
- A long list of conditions have been associated with osteoporosis in observational trials. Confounding is likely an issue in many of these studies.
- The table below lists risk factors for osteoporosis that have been largely validated and are included in the FRAX tool
Risk factors for osteoporosis included in the FRAX tool | |
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Risk factor | Comment |
Age |
|
Female (Menopause) |
|
Low BMI (< 20) |
|
Previous fracture |
|
Parental hip fracture |
|
Oral corticosteroids |
|
Current smoking |
|
Alcohol intake |
|
Rheumatoid arthritis |
|
Chronic diseases (secondary osteoporosis) |
|
- OSTEOPENIA
- Osteopenia is a milder form of bone loss than osteoporosis. In DXA scanning, osteopenia is defined as a T-score between -1.0 and -2.5.
- The risk of fracture varies widely in patients with osteopenia. In general, fracture risk is less than that of osteoporosis, but still significant with about half of fractures attributable to weak bones occurring in patients with osteopenia. [1]
- The risks and benefits of pharmacological treatment in patients with osteopenia has not been studied extensively. One large study published in 2018 found that zoledronic acid for 6 years reduced the incidence of fractures in women with osteopenia. Subjects in the study had a median 10-year risk of hip fracture and osteoporosis-related fracture of 2.4% and 12%, respectively. That study is detailed here - zoledronic acid vs placebo in osteopenia.
- Current guidelines recommend treating patients with osteopenia who are at increased risk of fracture. Increased risk is defined as a 10-year risk of ≥ 3% for a hip fracture or ≥ 20% for major osteoporosis-related fracture based on the FRAX tool
- SCREENING
USPSTF osteoporosis screening recommendations |
---|
Women
|
Endocrine Society osteoporosis screening recommendations in men |
Men
|
- Rescreening
- Professional guidelines do not offer guidance on rescreening patients for osteoporosis
- A cohort study published in the NEJM in 2012 looked at the risk of osteoporosis in postmenopausal women ≥ 65 years of age based on their initial T-scores. Findings from that study are presented in the table below. A review article published in the JAMA in 2021 used data from that study and others to suggest on appropriate rescreening intervals based on initial T-scores and FRAX-calculated risk estimates. The second table shows those recommendations.
Estimated time interval for at least 10% of women in each group to transition to osteoporosis on BMD testing | |
---|---|
Initial BMD | Interval (95% CI) |
Normal (T-score -1.0 or higher) |
16.8 years (11.5–24.6) |
Mild osteopenia (T-score -1.01 to -1.49) |
17.3 years (13.9 – 21.5) |
Moderate osteopenia (T-score -1.50 to -1.99) |
4.7 years (4.2 – 5.2) |
Advanced osteopenia (T-score -2.0 to -2.49) |
1.1 years (1.0 – 1.3) |
Suggested rescreening intervals based on initial BMD and FRAX estimated risk (For patients who meet criteria in different intervals, use the shortest interval) |
|||
---|---|---|---|
Initial BMD | 10-year major fracture risk | 10-year hip fracture risk | Suggested rescreening interval |
> -1.0 | < 10% | < 0.8% | > 10 years |
-1.0 to -1.4 | 10 - 14% | 0.8 - 1.4% | 5 - 10 years |
-1.5 to -1.9 | 15 - 19% | 1.5 - 2.2% | 3 - 5 years |
-2.0 to -2.4 | N/A | 2.3 - 2.9% | < 3 years |
- DIAGNOSIS
- DXA scanning
- DXA stands for dual-energy x-ray absorptiometry. DXA is an imaging technique where X-rays are aimed at a person's bones. The absorption of the X-ray beams by the bone is measured, and from this, bone mineral density (BMD) can be estimated.
- The hips and lumbar spine are the most accurate areas for assessing BMD
- BMD units are reported as grams of mineral per cm². They are also expressed as T-scores and Z-scores. The T-score represents the number of standard deviations that the person's BMD deviates from that of a healthy young adult. The Z-score represents the number of standard deviations that a person's BMD deviates from an age-, race- and sex-matched control.
- T-scores are used for diagnosis and treatment decisions in most cases. In premenopausal women, men < 50 years of age, and children, T-scores have not been validated, and Z-scores should be used. In these patients, the International Society for Clinical Densitometry (ISCD) recommends that a Z-score ≤ -2.0 be used to define low BMD. [1,2]
- T-score and Z-score definitions are presented in the table below
Classification criteria for BMD T-scores | |
---|---|
Category | T-score |
Normal | -1 or above |
Osteopenia | -1.0 to -2.5 |
Osteoporosis | -2.5 or below |
Classification criteria for Z-scores | |
---|---|
Category | Z-score |
Within expected range | greater than -2.0 |
Below expected range for age | -2.0 and below |
- X-ray
- Vertebral fractures are considered diagnostic for osteoporosis, and they are also an indication for pharmacological treatment
- Most vertebral fractures are asymptomatic and go undiagnosed
- Vertebral fractures can be diagnosed with lateral X-rays of the thoracic and lumbar spine. Many DXA machines can also assess for vertebral fractures using a technology called lateral vertebral fracture assessment (VFA). [2]
- The International Osteoporosis Foundation recommends vertebral imaging be considered in the following patients:
- All women age 70 and older and all men age 80 and older if BMD T-score at the spine, total hip, or femoral neck is ≤ −1.0
- Women age 65 to 69 and men age 70 to 79 if BMD T-score at the spine, total hip, or femoral neck is ≤ −1.5
- Postmenopausal women and men age 50 and older with any of the following risk factors:
- Low-trauma fracture during adulthood (age 50 and older)
- Historical height loss of 1.5 inches (4 cm) or more
- Prospective height loss of 0.8 inch (2 cm) or more
- Recent or ongoing long-term glucocorticoid treatment [2]
- SECONDARY CAUSES
Medical conditions associated with osteoporosis | |
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Condition | Comment |
Hyperparathyroidism |
|
Cushing's syndrome |
|
Gastrointestinal disorders |
|
Hyperthyroidism |
|
End-stage kidney disease |
|
Hyperprolactinemia |
|
Hemochromatosis |
|
Athletic amenorrhea |
|
Monoclonal gammopathies |
|
Medications associated with osteoporosis | |
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Medication | Comment |
Anticonvulsants |
|
Aromatase inhibitors |
|
Depo Provera® |
|
Glucocorticoids |
|
Lithium |
|
SGLT2 inhibitors |
|
Proton pump inhibitors |
|
Glitazones |
|
Thyroid hormone replacement |
|
Immunomodulators |
|
GnRH agonists |
|
- TREATMENT AND MONITORING
Endocrine Society 2019 Osteoporosis Treatment Recommendations for Postmenopausal Women |
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WHOM TO TREAT |
Step 1 - Determine patient's fracture risk
Step 2 - Assign risk category below
|
CHOICE OF THERAPY |
Low risk
High risk or Very high risk
Patients who cannot tolerate the above recommended therapies
|
MONITORING THERAPY |
Oral bisphosphonate
Denosumab
Teriparatide or abaloparatide
|
DURATION OF THERAPY |
Bisphosphonate
|
Endocrine Society 2012 Osteoporosis Treatment Recommendations for Men |
---|
WHOM TO TREAT |
Treat men with any of the following
|
CHOICE OF THERAPY |
One of the following
|
MONITORING THERAPY |
|
- Glucocorticoid-induced osteoporosis
- During the first 3 months of glucocorticoid therapy, a rapid decline in bone mineral density is often seen. The decline peaks around 6 months and then continues at a slower pace with continued use. Doses of prednisolone or equivalent as low as 2.5 mg/day have been associated with increased fracture risk in some studies, while others have found no increased risk with doses under 5 mg/day. [7]
- Recommendations from the American College of Rheumatology for the treatment and prevention of glucocorticoid-induced osteoporosis are presented below
- VITAMIN D
- Vitamin D plays an important role in calcium regulation and bone health. See the links below for information on vitamin D.
- CALCIUM
- Physiology
- Calcium and phosphate combine to form hydroxyapatite, the mineral that gives bone strength. Ninety-nine percent of body calcium is found in bones and 1% is in the extracellular space. Extracellular calcium plays an important role in nerve conduction and muscle contraction so serum levels are tightly regulated (see calcium regulation). When dietary calcium is inadequate to maintain proper serum calcium levels, calcium is mobilized from bone through bone resorption. Chronic bone resorption can lead to decreased bone density and fractures. [1]
NAM recommended daily dietary allowance for calcium | ||
---|---|---|
Age | Sex | Calcium (elemental) |
0 - 6 months | M/F | 200 mg |
7 - 12 months | M/F | 260 mg |
1 - 3 years | M/F | 700 mg |
4 - 8 years | M/F | 1000 mg |
9 - 18 years | M/F | 1300 mg |
19 - 50 years | M/F | 1000 mg |
51 - 70 years | M | 1000 mg |
51 - 70 years | F | 1200 mg |
≥ 71 years | M/F | 1200 mg |
Calcium content of dairy products | |
---|---|
Food | Calcium (mg) |
Milk (8 oz) | 300 mg |
Yogurt (6 oz) | 300 mg |
Cheese (1 oz or cubic in.) | 200 mg |
Fortified foods | 80 - 1000 mg (varies widely) |
- Calcium supplements
- Patients who may have a dietary deficiency of calcium may take supplements so that they meet their recommended dietary intake
- It's important to note that there is no conclusive evidence that calcium supplementation prevents fractures or has a significant effect on BMD [10,11]
- Calcium supplements are detailed in the table below. Calcium carbonate and calcium citrate are the most commonly used supplements.
Calcium supplement | % elemental calcium | Other |
---|---|---|
Calcium carbonate (ex. Caltrate®) | 40% |
|
Calcium acetate | 25% |
|
Calcium citrate (ex. Citracal®) | 21% |
|
Calcium lactate | 13% |
|
Calcium gluconate (ex. Cal-Glu®) | 9% |
|
- BIBLIOGRAPHY
- 1 - PMID 21224201 AACE OP GL
- 2 - PMID 25182228 IOF GL
- 3 - USPSTF website
- 4 - PMID 22675062 Endocrine society recs in men
- 5 - PMID 21083387 Bisphosphonates for OP
- 6 - PMID 21542743 Femoral fx risk
- 7 - PMID 20662044 ACR recs
- 8 - PMID 16837676 Ruth trial
- 9 - PMID 25423325 Ospemifene MOA
- 10 - PMID 26420598 - Calcium intake and BMD
- 11 - PMID 26420387 - Calcium intake and fracture risk
- 12 - PMID 28585410 - 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis
- 13 - PMID 28492856 - Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians, Annals of Internal Medicine (2017)
- 14 - PMID 30907953 - Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab (2019)
- 15 - PMID 34698797 - Serial Bone Density Measurement for Osteoporosis Screening, JAMA (2021)
- 16 - PMID 36592456 - Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians, Ann Intern Med (2023)