3 Pathogenesis

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. Either bone resorption is excessive, or bone formation is diminished. Bone matrix is manufactured by the osteoblast cells, whereas bone resorption is accomplished by osteoclast cells. Trabecular bone is the sponge-like bone in the center of long bones and vertabrae. Cortical bone is the hard outer shell of bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active, more subject to bone turnover, to remodeling. Long before any overt fractures occur, the small spicules of trabecular bone break and are reformed in the process known as remodeling. Bone will grow and change shape in response to physical stress. The bony prominences and attachments in runners are different in shape and size than those in weightlifters. It is an accumulation of fractures in trabecular bone that are incompletely repaired that leads to the manifestation of osteoporosis. The common osteoporotic fracture sited, the wrist, the hip and the spine, have a relatively high trabecular bone to cortical bone ratio. These areas rely on trabecular bone for strength.

Low peak bone mass is important in the development of osteoporosis. Bone mass peaks in both men and women between the ages of 25 and 35, thereafter diminishing. Achieving a higher peak bone mass through exercise and proper nutrition during adolescence is important for the prevention of osteoporosis.

Bone remodeling is heavily influenced by nutritional and hormonal factors. Calcium and Vitamin D are nutrients required for normal bone growth. Parathyroid hormone regulates the mineral composition of bone, with higher levels causing resorption of calcium and bone. Glucocorticoid hormones cause osteoclast activity to increase, causing bone resorption. Calcitonin, estrogen and testosterone increase osteoblast activity, causing bone growth. The loss of estrogen following menopause causes a phase of rapid bone loss. Similarly, testosterone levels in men diminish with advancing age and are related to male osteoporosis.

Physical activity causes bone remodeling. People who remain physically active throughout life have a lower risk of osteoporosis. Conversely, people who are bedridden are at a significantly increased risk. Physical activity has its greatest impact during adolescence, affecting peak bone mass most. In adults, physical activity helps maintain bone mass, and can increase it by 1 or 2%.

Lastly, osteoporosis on its own would not be a significant disease, were it not for the falls which precipitate fractures. Age-related sarcopenia , or loss of muscle mass, loss of balance and dementia contribute greatly to the increased fracture risk in patients with osteoporosis. Physical fitness in later life is associated more with a decreased risk of falling than with an increased bone mineral density.

4 Risk Factors

Risk Factors for Osteoporosis Fracture

• Nonmodifiable
  • Personal history of fracture as an adult
  • History of fracture in first-degree relative
  • Female sex
  • Advanced age
  • Caucasian race
  • Dementia
• Potentially modifiable
  • Current cigarette smoking
  • Intake of soft drinks containing phosphoric acid at any age
  • Low body weight <58 kg (127 lb)
  • Estrogen deficiency
  • Early menopause (<45 years) or bilateral oophorectomy
  • Prolonged premenstrual amenorrhea (>1 year)
  • Low calcium intake
  • Alcoholism
  • Impaired eyesight despite adequate correction
  • Recurrent falls
  • Inadequate physical activity
  • Poor health/frailty

Osteoporosis Risks

5 Natural History

Today, most cases of osteoporosis are diagnosed before symptoms develop. This is due to widespread screening for osteoporosis using the DEXA scan. With treatment, bone mineral density increases, and fracture risk decreases.

In the absence of treatment, overt osteoporosis is heralded by a fracture. Some fractures, like vertebral compression fractures or sacral insufficiency fractures, may not be apparent at first, appearing to patient and physician as a very bad back ache or completely without symptoms. Hip fractures and wrist fractures are more obvious.

Hip fractures are responsible for the most serious consequences of osteoporosis. In the United States, osteoporosis causes a predisposition to more than 250,000 hip fractures yearly. It is estimated that a 50-year-old white woman has a 17.5% lifetime risk of fracture of the proximal femur. The incidence of hip fractures increases each decade from the sixth through the ninth for both women and men for all populations. The highest incidence is found among those men and women ages 80 or older.

An estimated 700,000 women have a first vertebral fracture each year. The lifetime risk of a clinically detected symptomatic vertebral fracture is about 15% in a 50-year-old white woman.

Distal radius fractures, usually of the Colles ' type, are the third most common type of osteoporotic fractures. In the United States, the total annual number of Colles' fractures is about 250,000. The lifetime risk of sustaining a Colles' fracture is about 16% for white women. By the time women reach age 70, about 20% have had at least one wrist fracture.

6 Diagnosis

Dual Energy X-ray Absorptiometry is considered diagnostic for osteoporosis when bone mineral density (BMD) is under 2.5.

In order to differentiate between the possible causes of osteoporosis, blood tests and X-rays are usually done to rule out cancer with metastasis to the bone, multiple myeloma, Cushing's disease and the other causes mentioned above.

Diagnosis of Osteoporosis

7 Treatment

Patients at risk for osteoporosis (e.g. steroid use) are generally treated with Vitamin D and calcium supplements. In renal disease, a different form of Vitamin D (D₃) is used, as the kidney cannot adequately synthesise D3 from precursors.

In osteoporosis (or a very high risk), bisphosphonate drugs are prescribed. The most often prescribed bisphosphonate is alendronate (Fosamax®) 10 mg a day or 70 mg once a week. Other commonly used treatments include risedronate (Actonel) and raloxifene (Evista).

Recently, teriparatide (Forsteo®, recombinant parathyroid hormone) has been shown to be effective in osteoporosis, either alone or together with alendronate.

Changes to lifestyle factors and diet are also recommended; the "at-risk" patient should include up to 1000mg of calcium in their diet (1500mg for a post-menopausal woman), which is roughly 3 servings of foodstuffs high in calcium daily. Thirty minutes of weight-bearing exercise such as walking or jogging, three times a week, have been shown to increase bone mineral density, and reduce the risk of falls by strengthening the major muscle groups in the legs and back.

Osteoporosis Treatment

8 Prognosis

Patients with osteoporosis are at a high risk for additional fractures (the best predictor of fracture is a previous fracture). Treatment can improve fracture risk considerably.

Fractures can lead to decreased mobility and an additional risk of deep venous thrombosis and/or pulmonary embolism. Vertebral fractures can lead to severe chronic pain of neurogenic origin, which can be hard to control.

Although osteoporosis patients have an increased mortality rate due to the complications of fracture, most patients die with the disease rather than of it.

9 Future directions

As more research takes place in the biological mechanisms of accellerated bone loss, new therapeutic agents are identified and introduced. Recent research seems to indicate that pharmacological inhibition of lipooxygenase 15 type 2 (see eicosanoid for some background) may produce new drugs to prevent and treat osteoporosis.

10 External Links

Dr. Susan Ott's great site on osteoporosis

Endocrinology

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