Osteoporosis

Template:TOC-right Osteoporosis is "reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (osteoporosis, postmenopausal) and age-related or senile osteoporosis."

Although more common in women, osteoporosis may occur in males.

Causes/etiology

Glucocorticoid drugs can cause osteoporosis.

Subclinical hypercortisolism may underly about 5% of cases of osteoporosis. These patients can be identified by serum cortisol levels greater than 50.0 nmol/L after a 1-mg overnight dexamethasone test.

Diagnosis

Diagnosis is made be bone densitometry, or by the presence of fragility fractures. However, high-trauma fractures also are associated with osteoporosis.

History and physical examination

A systematic review by the Rational Clinical Examination concluded that the best physical findings in women are:

• weight less than 51 kg
• tooth count less than 20
• rib-pelvis distance less than 2 finger breadths
• wall-occiput distance greater than 0 cm
• self-reported humped back

For men, the "MORES" clinical prediction rule uses age, weight, and history of chronic obstructive pulmonary disease to predict risk of a fracture with a number needed to screen of 279 to prevent one fracture:

• sensitivity = 93%
• specificity = 59%

Bone densitometry

Densitometry results are generally scored by two measures, the T-score and the Z-score. Scores indicate the amount one's bone mineral density varies from the mean. Negative scores indicate lower bone density, and positive scores indicate higher.

T-score

The T-score is a comparison of a patient's BMD to that of a healthy thirty-year-old. The criteria of the World Health Organization are:

• Osteoporosis is defined as -2.5 or lower, meaning a bone density that is two and a half standard deviations below the mean of a thirty year old woman.
• Osteopenia is defined as less than -1.0 and greater than -2.5
• Normal is a T-score of -1.0 or higher

Z-score

The Z-score is a comparison of a patient's BMD to the average BMD of their, sex, and race. This value is used in premenopausal women, men under aged 50, and in children.

Other tests

Screening patients for hypercortisolism with a 2-day, low-dose dexamethasone suppression test ( 0.5 mg of dexamethasone by mouth every 6 hours followed by measurement of serum cortisol at 9:00 a.m. 2 days after the first dose), may identify hypercortisolism in 10% of patients who have both T-scores of –2.5 or less and vertebral fractures.

Screening

Females

The US Preventive Services Task Force recommends that all women 65 years of age or older should be screened with bone densitometry. The Task Force recommends screening women 60 to 64 years of age who are at increased risk. The best risk factor for indicating increased risk is lower body weight (weight < 70 kg).

Clinical prediction rules are available to guide selection of women for screening. The Osteoporosis Risk Assessment Instrument (ORAI) may be the most sensitive strategy for detecting abnormal bone density. More recently, a clinical prediction rule for women developed from the WHO studies (http://hipcalculator.fhcrc.org/) is available to predict risk of a fracture over five years. Of note, the clinical prediction rule did not study the contribution of physical examination findings.

Males

A cost-benefit analysis concluded that "bone densitometry followed by bisphosphonate therapy for those with osteoporosis may be cost-effective for men aged 65 years or older with a self-reported prior clinical fracture and for men aged 80 to 85 years with no prior fracture."

A clinical practice guideline and systematic review by the American College of Physicians recommends "clinicians obtain DXA [dual-energy x-ray absorptiometry] for men who are at increased risk for osteoporosis and are candidates for drug therapy." However, the College did not define increased risk.

Treatment

It is not clear which medications are best for treating osteoporosis.

Calcium

A meta-analysis of randomized controlled trials concluded "Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older. For best therapeutic effect, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation)."

Antiresorptive medications

Bisphosphonates

Bisophosphonates may be cost-effective when the 10 year risk of fracture is 3% (see osteoporosis#prognosis below). Once yearly, intravenous zoledronic acid reduced second hip fractures in a randomized controlled trial of women after an initial hip fracture. In this trial, 19 patients had to be treated for one hip fracture to be prevented.

The effects of alendronate may continue through 10 years of treatment according to the FLEX randomized controlled trial which included women with T-scores of -1.6 or worse. However, the FLEX trial found increased wrist fractures with long term treatment. This increase may be due to "oversuppressing bone turnover that could, potentially, impair some of the biomechanical properties of bone. High doses of bisphosphonates result in accumulation of microdamage in the bones of dogs, but the relevance of these findings in terms of bone strength and clinical use is unclear."

Denosumab

Denosumab is a humanized monoclonal antibody that inhibits osteoclasts.

Anabolic medications

As opposed to antiresorptive drugs, anabolic drugs enhance bone formation.

Strontium Ranelate

Strontium Ranelate has both anti-resorptive and anabolic mechanisms.

Prognosis

The risk of fracture can be estimated by the WHO Fracture Risk Assessment Tool (http://www.shef.ac.uk/FRAX/tool.jsp?locationValue=9).

A bone mineral density of one standard deviation below age adjusted mean approximately doubles the risk of fracture.

See also

• Glucocorticoid