Osteoporosis

Osteoporosis

The World Health Organization (WHO) operationally defines osteoporosis as a bone density that falls 2.5 standard deviations (SD) below the mean for young healthy adults of the same gender—also referred to as a T-score of –2.5. Postmenopausal women who fall at the lower end of the young normal range (a T-score of >1 SD below the mean) are defined as having low bone density and are also at increased risk of osteoporosis

The epidemiology of fractures follows the trend for bone density loss. Fractures of the distal radius increase in frequency before age 50 and plateau by age 60, with only a modest age-related increase thereafter. In contrast, incidence rates for hip fractures double every 5 years after age 70. Hip fractures are associated with a high incidence of deep vein thrombosis and pulmonary embolism (20–50%) and a mortality rate between 5 and 20% during the year after surgery. Thoracic fractures can be associated with restrictive lung disease, whereas lumbar fractures are associated with abdominal symptoms including distention, early satiety, and constipation.

Chronic diseases with inflammatory components that increase skeletal remodeling, such as rheumatoid arthritis, increase the risk of osteoporosis, as do diseases associated with malabsorption. osteoporosis-related fractures are more common among women than men, presumably due to a lower peak bone mass as well as postmenopausal bone loss in women. a fracture in a person over 50 should trigger evaluation for osteoporosis.

Pathophysiology: although true bone density remains similar between sexes. Heritability estimates of 50–80% for bone density and size have been derived based on twin studies. In osteoporosis, Bone remodeling has two primary functions: (1) to repair microdamage within the skeleton to maintain skeletal strength, and (2) to supply calcium from the skeleton to maintain serum calcium. The mass of the skeleton remains constant after peak bone mass is achieved in adulthood. After age 30–45, however, the resorption and formation processes become imbalanced, and resorption exceeds formation. In trabecular bone, if the osteoclasts penetrate trabeculae, they leave no template for new bone formation to occur and, consequently, rapid bone loss ensues and cancellous connectivity becomes impaired

expert consensus panel has suggested that the accepted levels for serum 25-hydroxyvitamin D [25(OH)D] have been set too low, and that optimal targets for serum 25(OH)D are >75 nmol/L (30 ng/mL). To achieve this level for most adults requires intakes of 800–1000 units/day

Estrogen deficiency probably causes bone loss by two distinct but interrelated mechanisms: (1) activation of new bone remodeling sites, and (2) exaggeration of the imbalance between bone formation and resorption. The original National Osteoporosis Foundation guidelines recommend bone mass measurements in postmenopausal women, assuming they have one or more risk factors for osteoporosis in addition to age, gender, and estrogen deficiency. The guidelines further recommend that bone mass measurement be considered in all women by age 65, a position ratified by the U.S. Estrogen-deficient women at clinical risk of osteoporosis

Vertebral abnormalities on x-ray suggestive of osteoporosis (osteopenia, vertebral fracture)

Glucocorticoid treatment equivalent to 7.5 mg of prednisone, or duration of therapy >3 months

Primary hyperparathyroidism

Monitoring response to an FDA-approved medication for osteoporosis

Repeat BMD evaluations at >23-month intervals, or more frequently, if medically justified

Treatment should also be considered in postmenopausal women with risk factors, even if BMD is not in the osteoporosis range. It is important to consider the risk of fracture for individuals, including those whose BMD is within the premenopausal range. Risk factors (age, prior fracture, family history of hip fracture, low body weight, cigarette consumption, excessive alcohol, steroid use, and rheumatoid arthritis) can be combined with BMD to assess the likelihood of a fracture over a 5- or 10-year period. Treatment thresholds depend on cost-effectiveness analyses but will likely be ~1% per year of risk in the United States.

A careful history and physical examination should be performed to identify risk factors for osteoporosis. A low Z-score increases the suspicion of a secondary disease. Height loss > 2.5–3.8 cm (>1–1.5 in.) is an indication for radiography or vertebral fracture assessment by DXA to rule out asymptomatic vertebral fractures, as is the presence of significant kyphosis or back pain, particularly if it began after menopause. For patients who present with fractures, it is important to ensure that the fractures are not caused by an underlying malignancy.

Bone formation

Serum bone-specific alkaline phosphatase

Serum osteocalcin

Serum propeptide of type I procollagen

Bone resorption

Urine and serum cross-linked N-telopeptide

Urine and serum cross-linked C-telopeptide

Urine total free deoxypyridinoline

If a calcium supplement is required, it should be taken in doses 600 mg at a time, as the calcium absorption fraction decreases at higher doses. Calcium supplements containing carbonate are best taken with food since they require acid for solubility. Calcium citrate supplements can be taken at any time

Several controlled clinical trials of calcium plus vitamin D have confirmed reductions in clinical fractures, including fractures of the hip (~20–30% risk reduction.

Vit D: the Institute of Medicine recommends daily intakes of 200 IU for adults <50>70 years.