Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fractures.
Osteoporosis is a silent disease and does not produce any symptoms until the time of fracture. Osteoporosis is very common in postmenopausal women. Osteoporotic fragility fractures typically involve vertebrae, the femoral neck, and the distal radius but may occur in any other area.
In patients who are suspected of having undiagnosed secondary causes of osteoporosis, further work-up is warranted. The conditions that could present as osteoporosis include endocrine diseases such as hyperthyroidism, hyperparathyroidism, Cushing’s disease, and hypogonadism; malabsorption such as may occur due to celiac disease; and malignancies such as multiple myeloma.
In the US, more than 10 million people have osteoporosis; more than 1.5 million osteoporosis-related fractures occur each year. The lifetime risk for osteoporosis-related fractures is about 40% in Caucasian women age 50 years and above and 13% in Caucasian men of similar age.
Pathology and pathophysiology
The principal cell types of bone are osteoclasts, osteoblasts, and osteocytes:
- Osteoclasts, the cells responsible for resorption of bone, are derived from hematopoietic stem cells.
- Osteoblasts, derived from local mesenchymal cells, are responsible for bone formation.
- Osteocytes, also derived from mesenchymal cells, are the most numerous cells in the bone and may be involved in signaling to osteoclasts and osteoblasts and help regulate their functioning.
In the normal adult bone, new bone laid down by osteoblasts exactly matches osteoclastic bone resorption; that is, bone formation and bone resorption are closely coupled.
Key regulators of osteoclastic bone resorption include RANK ligand (RANKL) and its receptor, RANK, and osteoprotegerin (OPG). Osteoblasts express RANKL, which interacts with its receptor RANK on osteoclasts, promoting differentiation. OPG is secreted by osteoblasts and stromal cells and blocks interaction between RANKL and RANK by binding to RANKL competitively.
Osteoporosis occurs as a result of an alteration in bone turnover from an imbalance between the activity of osteoclasts and osteoblasts.
Secondary causes of osteoporosis includes endocrine diseases (hyperthyroidism, hyperparathyroidism, Cushing’s disease, hypogonadism), genetic diseases (osteogenesis imperfecta), rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis), malabsrption (celiac disease, gastrectomy), and drugs (glucocorticoids, heparin, anticonvulsants, aromatase inhibitors).
Estrogen deficiency following menopause results in an imbalance in bone remodeling, with a substantial relative increase in bone resorption compared to bone formation. Estrogen influences the generation of osteoclast and osteoblast progenitors in the bone marrow: It has pro-apoptotic effects on osteoclasts and anti-apoptotic effects on mature osteoblasts and osteocytes.
The onset of cortical bone loss in women is closely tied to estrogen deficiency, attesting to the adverse effect of estrogen deficiency on skeletal homeostasis and its contribution to age-associated bone loss. However, a significant proportion of trabecular bone loss throughout life is age-related and estrogen-independent. The age-dependent loss of trabecular bone in the spine accelerates after menopause, as does the rate of fractures at the wrist, spine, and hip. Between menopause and the age of 75, women lose approximately 22% of their total body bone mineral. It has been estimated that 13.3% of this bone mineral loss is due to aging and 7.75% is due to estrogen deprivation. In the femoral neck, 14% of the loss is age-related and only 5.3% is due to relative estrogen deprivation.
Radiographic and laboratory findings
Dual-energy X-ray absorptiometry (DEXA) is the most widely used bone density measurement technique. In DEXA, bone mineral density is reported as a comparison to age-, race- and sex-matched reference ranges (Z score) and as a comparison to mean bone mass of young (30-year-old) adult normal individuals (T score). It can be used to measure bone mass at various sites, but the hip and spine are typically the measured locations.
The World Health Organization (WHO) defines osteoporosis as a T score < -2.5 and osteopenia as T score between -1 and -2.5.
Risk factors and prevention
The risk factors for osteoporosis include:
- Advanced age
- Female gender
- Caucasian or Asian ethnicity
- Family history
- Low calcium intake
- Low body weight
- Endocrine conditions (hyperthyroidism, hyperparathyroidism, hypogonadism)
- Rheumatic conditions (rheumatoid arthritis, ankylosing spondylitis)
- Drugs (glucocorticoids, heparin, anticonvulsants, aromatase inhibitors)
There are three components to the nondrug therapy of osteoporosis: diet, exercise, and cessation of smoking. An optimal diet for treatment (or prevention) of osteoporosis includes an adequate intake of calories (to avoid malnutrition), calcium, and vitamin D. Postmenopausal women (and older men) should take adequate supplemental elemental calcium (generally 500 to 1,000 mg/day) and 800 international units of vitamin D daily.
Exercise also has beneficial effects on bone mineral density (BMD) in premenopausal and postmenopausal women. A variety of exercise types, including resistance training, jogging, jumping, and walking, are effective.
Smoking cessation is recommended to all women with osteoporosis because smoking cigarettes accelerates bone loss. This may be mediated in part by acceleration of metabolism of estrogen.
The above measures should be adopted universally to reduce bone loss in postmenopausal women. Postmenopausal women with osteoporosis are at high risk for the disease should be considered for drug (or hormonal) therapy. Particular attention should be paid to treating women with a recent fracture, including hip fracture, because they are at high risk for a second fracture.
Drugs that reduce bone resorption (anti-resorptive) and drugs that increases bone formation (anabolic) are available. Anti-resorptive agents include bisphosphonates, selective estrogen receptor modulators, estrogen, and anti-RANKL. Teriparatide, a derivative of parathyroid hormone, is the only anabolic agent available on the market.
Bisphosphonate treatment is the most commonly used treatment for osteoporosis. In the Fracture Intervention Trial (FIT), one of the largest trials in postmenopausal women with low bone density, the two study arms compared daily alendronate and placebo.
- The vertebral fracture study arm included 2,027 women with a low femoral neck bone density (T-score <-2.1) and at least one vertebral fracture at baseline. Alendronate therapy increased femoral neck and spine BMD by 4.1% and 6.2%, respectively, and reduced the risk of vertebral fracture by approximately 50% and the risk of hip and wrist fractures by approximately 30%.
- The clinical fracture study arm included 4,432 postmenopausal women with a low femoral neck bone density (T-score <-1.6), but no vertebral fracture at baseline. Alendronate therapy (5 mg per day for 2 years followed by 10 mg per day for the remainder of the trial) increased bone mineral density and reduced the risk of vertebral fractures (diagnosed by X-ray) by 44% but did not significantly decrease the risk of hip, wrist, or all clinical fractures. However, in a subgroup of the subjects who had osteoporosis (baseline femoral neck T score of -2.5 or less), alendronate reduced the risk of hip fractures and all clinical fractures by 56% and 36%, respectively.
Adequate intake of calcium and vitamin D, adequate exercises, smoking cessation, and limitation of alcohol consumption can help prevent and are important adjunctive components of the treatment of osteoporosis.
Glucocorticoid use is one of the most common causes of drug-induced osteoporosis due to multiple detrimental effects on bones. First, glucocorticoids directly inhibit osteoblastic bone formation. Second, these drugs stimulate bone resorption by lowering calcium levels and increasing secretion of PTH. Glucocorticoids can cause significant bone loss and fractures within 6 months of therapy initiation.
Osteoporosis, fragility fracture
Skills and competencies
Understand diagnosis and treatment of osteoporosis