Osteoporosis

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
One of every eight hip fractures may be due to smoking of tobacco.

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.

Glucocorticoid drugs can cause osteoporosis.

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 using photon absorptiometry is 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 bone density 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 bone density to the average bone density 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.

Females
The US Preventive Services Task Force recommends screening women if:
 * 65 years of age or older
 * 60 to 64 years of age who are at increased risk using a tool such as the Osteoporosis Risk Assessment Instrument (ORAI. The best risk factor for indicating increased risk is lower body weight (weight < 70 kg).

The National Osteoporosis Foundation recommends screening women if:
 * 65 years of age or older
 * "Women in the menopausal transition if there is a specific risk factor associated with increased fracture risk such as low body weight, prior low-trauma fracture or high risk medication"
 * Fracture after age 50
 * "A condition (e.g., rheumatoid arthritis) or taking a medication (e.g., glucocorticoids in a daily dose ≥ 5 mg prednisone or equivalent for ≥ three months) associated with low bone mass or bone loss"
 * Low body weight

Clinical prediction rules are available to guide selection of women for screening. The Osteoporosis Self-Assessment Tool (OST) may be the most sensitive strategy for detecting abnormal bone density according to a meta-analysis in 2007. More recently, a clinical prediction rule for women developed from the WHI 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.

Unfortunately, all current guidelines and prediction rules ignore the role of risk factors for accidental falls.

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
The National Osteoporosis Foundation recommends treating women if:
 * T-score ≤ -2.5
 * Low bone mass (T-score between -1.0 and -2.5) and ≥ 3% 10-year hip fracture probability. This threshold was determined by a cost-benefit analysis.

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)."

Bisphosphonates
Bisophosphonates may be cost-effective when the 10 year risk of fracture is 3% (see osteoporosis 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.

Alendronate reduces clinical fractures by 36% in women with osteoporosis. The benefit is stronger for women with existing vertebral fractures.

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

FRAX tool
The risk of fracture can be estimated by the Fracture Risk Assessment Tool (FRAX). This tool was recommended by the WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level during their 2004 meeting. Interpretation of the ability of the FRAX is hindered by their publications not following guidlines for reporting of studies of diagnostic tests as as the STARD.