osteoprosis

Osteoporosis
Definition
Primary osteoporosis is a metabolic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and increased fracture risk. It also has normal mineral-to-collagen ratio. Primary osteoporosis represents bone mass loss that is unassociated with any other illness and is related to aging and loss of the gonadal function in women and the aging process in men

Secondary osteoporosis can result from a variety of the chronic conditions that significantly contribute to bone mineral loss, or it can result from the effects of medications and nutritional deficiencies
• Anorexia nervosa
• Chronic liver disease
• Chronic renal insufficiency
• Cushing s syndrome
• Disseminated carcinomatosis
• Ehlers-Danlos syndrome
• Hemochromatosis
• Homocystinuria
• Hypercalciuria
• Hyperparathyroidism
• Hyperprolactinemia
• Hyperthyroidism
• Hypophosphatasia
• Marfan syndrome
• Mastocytosis
• Multiple myeloma
• Osteogenesis imperfect
• Renal tubular acidosis

Medications
• Cyclosporine
• Excess thyroid hormones
• GnRH agonists
• Heparin
• Methotrexate
• Phenobarbital
• Phenothiazines
• Phenytoin
• Steroids
Other Causes
• Athletic amenorrhea
• Pregnancy
• Tobacco use
The World Health Organization (WHO) defines osteoporosis as bone density that is 2.5 standard deviations (SDs) or more below the young adult mean value (T-score <?2.5). Patients with bone density between 1 and 2.5 SDs below average (T-score ?1 to ?2.5) are said to have osteopenia. Decreased bone density imparts increased risk for bone fracture. Every 1 SD decrease in bone density of the spine increases risk for new vertebral fracture by factor of 2.0 to 2.4.

Prevalence
Osteoporosis is the most common metabolic bone disease. About 54% of postmenopausal white women in the United States have osteopenia and 30% have osteoporosis. Men and nonwhite women at risk add 30 million to 54 million affected persons in the United States.
Pathophysiology
Basic mechanisms responsible for development of osteoporosis are poor bone mass acquisition during growth and development and accelerated bone loss in the period after peak bone mass is achieved. Both processes are modulated by environmental and genetic factors
Approximately half of the bone mass is accumulated during pubertal development. This is associated with the increase in sex hormone levels and is almost completed with closure of the end plates. There is only minimal additional accumulation of the bone minerals during the next 5 to 15 years (skeletal consolidation). Peak bone mass is achieved during the third decade of life.
Bone loss, in contrast, appears to be mostly determined by environmental factors (nutritional, behavioral, and medications). However, genetic factors also play a role, mostly acting on a person s estrogen status

Important nutritional factors include dietary calcium intake, Vitamin D status, protein intake, and caloric intake. Phosphorus, vitamins C and K, copper, zinc, and manganese also play a role.
Among several medications glucocorticoids are the most important cause of bone loss (mostly trabecular). Fractures occur most commonly in vertebrae, ribs, and the ends of the long bones. Bone loss occurs very rapidly and may be as high as 20% during the first year of steroid use. The incidence of osteoporotic fractures in patients taking corticosteroids for more than 6 months is 30% to 50%. The dose of steroid that is detrimental to BMD in most people appears to be more than 7.5 mg of prednisone daily.
Female sex hormones (estrogens) are mandatory for acquisition of the peak bone mass and for maintenance of bone in women and men. Estrogen deficiency is considered a principal cause of postmenopausal osteoporosis. It might play important role in male osteoporosis as well. Risk factors for low BMD are summarized
Risk Factors Associated with Development of Osteoporosis
Not Modifiable
• Age
• Calcium deficient diet
• Family history of osteoporosis
• Low body weight
• Nulliparity
• Race (white or Asian)
• Use of medications
Modifiable
• Estrogen-deficient states
• Excessive alcohol intake
• Sedentary lifestyle
• Smoking
Signs and symptoms
The clinical expression of osteoporosis is a skeletal fracture. Vertebral fracture is the most common. Many patients (up to two thirds) remain asymptomatic after compressive vertebral fracture, and osteoporosis is diagnosed accidentally on the x-rays taken for other reasons. Incidence of new fracture has been estimated to be 19% in the year after the initial fracture.
Diagnosis
History and physical examination are important for identifying secondary causes of osteoporosis and to record behavioral risk factors, use of medications, and presence of signs and symptoms of osteoporotic complications. Use of risk factors as a prescreening device to select patients for further diagnostic procedures is inefficient and fails to identify a substantial portion of patients who have osteoporosis
Laboratory evaluation should be aimed toward diagnosis of secondary osteoporosis
Assessment of bone metabolism using markers of bone turnover can yield useful information and guide management decisions in some cases
Bone Density Measurements
Although diagnosis of osteoporosis is clinical, BMD must be measured to establish the diagnosis. The American Association of Clinical Endocrinologists lists indications for BMD determination:
• Perimenopausal or postmenopausal women who are willing to accept therapeutic or preventive interventions if osteoporosis diagnosed
• Persons whose x-ray findings suggest osteoporosis
• Persons starting or receiving long-term glucocorticoid therapy if therapeutic or preventive intervention is acceptable
• Persons with asymptomatic primary hyperparathyroidism in whom evidence of bone mineral loss would result in parathyroidectomy
• Persons treated for osteoporosis as a tool for monitoring response to therapy
Quantitative computed tomography (QCT) is only method able to measure true (volumetric) bone density, expressed as g/cm3. However, QCT is seldom used due to expense, higher radiation dose, and lower reproducibility than DEXA
Preventive Measures
General preventive measures against osteoporosis should be emphasized whenever possible. Adequate dietary calcium intake is one of the mainstays The needs may be met through a diet rich in calcium (e.g., milk, dairy products, calcium-fortified fruit juices) or by use of calcium supplements. Patients with untreated hypercalciuria should not take calcium supplements because of the risk of renal calculi. Vitamin D should be prescribed whenever there is suspicion of inadequate intake and particularly in elderly patients. About 800 IU/day is considered sufficient. Good nutrition with adequate caloric and protein intake should be promoted.
Use of tobacco and excessive alcohol use should be strongly discouraged. Regular exercise is integral for development of the skeleton during growth and development and might slow bone loss in the elderly. In addition, it promotes agility, flexibility, and strength, possibly preventing falls
Medications
Selective Estrogen-Receptor Modulators
Selective estrogen-receptor modulators (SERMs) are a group of medications that are useful in treating osteoporosis and that may be free of undesirable estrogen effects on reproductive tissues. They consist of tissue-selective receptor agonists raloxifene and tamoxifen, which have both estrogen agonist and antagonist properties. Raloxifene has estrogen-like activity on estrogen receptors in bone and cardiovascular tissue but not in endometrium and breast. Raloxifene preserves bone density, decreases serum total cholesterol level, and inhibits aortic accumulation of cholesterol. It does not cause endometrial or breast tissue hyperplasia
Bisphosphonates
Bisphosphonates are medications that inhibit bone resorption and have minimal side effects. After administration they attach to bone surfaces. During osteoclast resorption of the bone, bisphosphonates are released and prevent osteoclast activity. Bisphosphonates are widely used for prevention and treatment of osteoporosis, as well as hypercalcemia of malignancy e.g[
Alendronate Fosamax
Risedronate Actonel
Etidronate Didronel
Tiludronate Skelid
Pamidronate
Although rare, pill-induced esophagitis and ulcers can occur, and can be severe enough to warrant hospitalization and cause esophageal stricture. Hence, alendronate should not be given to patients with active upper GI disease
Calcitonin
Calcitonin is used in injection form (SC or IM) and as intranasal spray. Calcitonin injections are shown to increase BMD in the spine and reduce vertebral fracture better than calcium alone. Calcitonin has a significant analgesic effect on bone pain by an unknown mechanism, and it might have potential for reducing the pain of vertebral fracture in the acute setting.
Anabolic Therapy
Recombinant human PTH (hrPTH) is anabolic therapy. Given as a once-daily SC injection in humans, it has demonstrated a marked increase of BMD of the lumbar spine and hip. Vertebral fractures were reduced about 70% and nonvertebral fractures were reduced about 50% in studies. hrPTH is approved for use up to 24 months.
Formation - s timulating a gents
Teriparatide and parathyroid hormone — These agents have good
evidence for their abilities to increase bone formation (and later
bone resorption) with an improvement in bone mass and structure,
particularly in trabecular bone such as the vertebrae, with
reductions in spine fracture risk
Alternative a gents
Strontium ranelate — Strontium ranelate been shown to signifi -
cantly reduce vertebral and non - vertebral fracture risk in postmenopausal
women. The precise mechanism(s) of action remains unclear