Approach to osteoporosis

Most common causes of osteoporosis include aging, sex hormone deficiency, alcoholism, smoking, long-term proton pump inhibitor therapy and high-dose..

Essential of diagnosis

Fracture propensity of spine, hip, pelvis, and wrist from depletion of bone matrix with subsequent demineralization. Asymptomatic until a fracture has occurred. Serum PTH, calcium, phosphorus, and alkaline phosphatase usually normal and serum 25-hydroxyvitamin D levels often low as a comorbid condition. Most common causes of osteoporosis include aging, sex hormone deficiency, alcoholism, smoking, long-term proton pump inhibitor therapy and high-dose glucocorticoid administration.

Demographics: (1) Clinically evident in middle life and beyond. (2) Develops frequently in hypogonadal men. (3) White women aged ≥ 50 years (who do not receive estrogen replacement) have a 46% risk of sustaining an osteoporotic fracture during their lives.

NPS-adv

Assessment

Symptoms and signs

Usually asymptomatic until fractures occur.
May present as back pain of varying degrees of severity or as spontaneous fracture or collapse of a vertebra.
Loss of height common.
Fractures of femoral neck and distal radius also common.
Once osteoporosis is identified, careful history and physical examination are required to determine its cause.

Diagnosis

Differential diagnosis

Rickets in childhood (e.g. consequence of vitamin D deficiency)
Osteomalacia in adulthood (inadequate mineralization of existing bone matrix [osteoid]).
Plasma cell myeloma (formerly multiple myeloma).
Metastatic cancer.
Paget disease of bone.
Renal osteodystrophy.

Laboratory tests

In cases of primary osteoporosis, the following tests are normal: blood urea nitrogen, creatinine, albumin, serum calcium, phosphate and PTH. Alkaline phosphatase usually normal but may be slightly elevated, especially following fracture. Hypophosphatasia may be present when value is low (< 40 units/L in adults).

Complete blood count is obtained and is usually normal. For patients with anemia, further screening is required, including a SPEP to screen for myeloma and intestinal malabsorption screening, where indicated. Vitamin D deficiency is very common. Testing for thyrotoxicosis and hypogonadism may be required. Screen for celiac disease with serum IgA anti-tissue transglutaminase antibodies.

Imaging studies

Radiographs of spine and pelvis may show demineralization; in skull and extremities, demineralization is less marked. Radiographs of spine may show compression of vertebrae. Dual-energy x-ray absorptiometry (DXA) is quite accurate and delivers negligible radiation. Quantitative CT delivers more radiation but is highly accurate.

Osteoporosis: Bone densitometry T score ≤ –2.5
Osteopenia: T score ≤ –1.0 to –2.5

Diagnostic procedures

Fracture Risk Assessment Tool (FRAX) was developed by the World Health Organization to better predict an individual's 10-year risk of hip or other major osteoporotic fracture. Takes into consideration age, sex, ethnicity, bone mineral density, and other risk factors. Available for use online: www.shef.ac.uk/frax/.

Medications

Oral vitamin D₃ (cholecalciferol)

As a universal supplement of 800–2000 international units/day or in doses titrated to achieve serum levels of 25-hydroxyvitamin D ≥ 20 ng/mL (50 nmol/L). Serum levels should be maintained ≥ 30 ng/mL (75 nmol/L) for patients "at risk" such as pregnant women, older adults and persons with osteoporosis or fragility fractures. Early observational data shows adverse outcomes (increased heart disease and all-cause mortality) when 25-OHD serum levels are > 50 ng/mL (125 nmol/L). Therefore, optimal therapeutic range for 25-OHD serum levels appears to about 30–50 ng/mL (75–125 nmol/L).

Calcium intake

Recommended total elemental calcium intake is at least 1000 mg/day for all adults and 1200 mg/day for postmenopausal women and men over age 70 years. Calcium citrate does not require acid for absorption and is preferred for patients receiving acid blockers. Calcium carbonate should be taken with food to enhance calcium absorption.

Sex hormone replacement

Can prevent osteoporosis in hypogonadal women and men. Not effective for established osteoporosis. Low-dose transdermal systemic estrogen prevents osteoporosis in women with hypogonadism. Testosterone replacement therapy prevents osteoporosis in men with severe testosterone deficiency.

Bisphosphonates

Increase bone density, reduce fracture risk and prevent glucocorticoid-induced osteoporosis. Take bisphosphonates in morning with ≥ 8 oz water, at least 40 minutes before any other food or liquid. Must remain upright for 30 minutes after taking to reduce risk of pill-induced esophagitis. All patients taking bisphosphonates should receive oral calcium salt supplements (500–1000 mg/day) and oral vitamin D3 (starting at 1000 units/day). Examples:

Alendronate, 70 mg every week orally.
Risedronate, 150 mg tablet orally once monthly.
Ibandronate sodium, 150 mg once monthly orally.
Pamidronate (30–60 mg by slow intravenous infusion in normal saline solution every 3–6 months) or zoledronate (2–5 mg intravenously over at least 15–30 min every 12 months if oral bisphosphonates cannot be tolerated.

Estrogen, raloxifene, or bazedoxifene for women with hypogonadism

Raloxifene, 60 mg once daily orally decreases risk of vertebral, but not nonvertebral, fractures.
Bazedoxifene, selective estrogen receptor modulator (SERM) that is available as a fixed-dose combination medication with conjugated estrogens (0.45 mg/20 mg). FDA-approved for the prevention of osteoporosis in postmenopausal women with an intact uterus. Unlike raloxifene, it has not been shown to reduce the risk of breast cancer. Long-term use may increase risk of thromboembolic disease.

Teriparatide

Stimulates the production of new collagenous bone matrix, particularly in vertebral trabecular bone, which must be mineralized. Patients must have sufficient intake of vitamin D and calcium. Administer 20 mcg/day subcutaneously for 2 years, then discontinue and substitute a bisphosphonate. Teriparatide may also be used to promote healing of atypical femoral chalkstick fractures associated with bisphosphonate therapy. Avoid teriparatide in patients with:

Increased risk of osteosarcoma.
Hypercalcemia.

Use teriparatide with caution in patients taking corticosteroids and thiazide diuretics along with oral calcium supplementation therapy because hypercalcemia may develop.

Abaloparatide

Stimulates the production of new collagenous bone matrix, particularly in vertebral trabecular bone, which must be mineralized. Patients must have sufficient intake of vitamin D and calcium. Dosage: 80 mg daily subcutaneously for 2 years, then discontinue and substitute a bisphosphonate. Abaloparatide may also be used to promote healing of atypical femoral chalkstick fractures associated with bisphosphonate therapy. Avoid in patients with

Increased risk of osteosarcoma.
Hypercalcemia.

Use abaloparatide with caution in patients taking corticosteroids and thiazide diuretics along with oral calcium supplementation therapy because hypercalcemia may develop.

Denosumab (Prolia)

Dose 60 mg subcutaneously every 6 months. Usually administered for a 3- to 5-year course. Its efficacy is comparable to bisphosphonates. With prolonged use, it predisposes to atypical femoral fractures and osteonecrosis of the jaw.

Calcitonin therapy

Reduces the incidence of vertebral fractures, but its effect upon nonvertebral fractures has not been established. Much less effective than other treatments; if calcitonin is administered, other more effective treatments for osteoporosis should be given simultaneously. Long-term therapy increases the risk of liver cancer but reduces the risk of breast cancer. Used primarily for its analgesic effect for the pain of acute osteoporotic vertebral compression fractures. Calcitonin therapy is ineffective for chronic pain.

Nasal spray of calcitonin-salmon (Miacalcin) ㅡ Available in 2-mL metered-dose bottles containing 2200 units/mL. Usual dose is one puff (0.09 mL, 200 international units) once daily, alternating nostrils. Nasal symptoms such as rhinitis and epistaxis occur commonly. Other less common adverse reactions include flu-like symptoms, allergy, arthralgias, back pain, and headache.

THERAPEUTIC PROCEDURES..

Diet adequate in protein, total calories, calcium, and vitamin D.
Discontinue or reduce doses of corticosteroids, if possible.
High-impact physical activity (eg, jogging), stair-climbing, and weight training increase bone density.
Fall-avoidance measures.
Avoid alcohol and smoking.
Percutaneous vertebroplasty or kyphoplasty may be considered for patients with vertebral compression fractures who do not respond to conservative pain management. However, no prospective randomized study has adequately compared the effectiveness of these orthopedic procedures compared to conservative therapy.

Follow-up, complications and prognosis

DXA bone densitometry every 2–3 years. Monitor patients taking corticosteroids or thiazides or who have kidney disease for development of hypercalcemia when given calcium supplements and reduce bisphosphonate dosage in chronic kidney disease, and monitor serum phosphate.

Complications

Oral bisphosphonates can cause esophagitis, gastritis, and abdominal pain. Oral and intravenous can cause fatigue, bone, joint, muscle pain, or osteonecrosis of the jaw. Pains can be migratory or diffuse, mild to incapacitating. Onset of pain occurs 1 day to 1 year after therapy is initiated, with a mean of 14 days. Pain can be transient, lasting several days and resolving spontaneously, but typically recurs with subsequent doses. Most experience gradual pain relief when medication is stopped.
Raloxifene increases the risk for thromboembolism. It aggravates hot flashes. may cause weight gain, depression, insomnia.
Teriparatide cause orthostatic hypotension, leg cramps. Hypercalcemia (if taken along with corticosteroids, thiazide diuretics, and calcium supplementation). Must not be given to patients with Paget disease or a history of osteosarcoma or chondrosarcoma.
Nasal calcitonin-salmon can cause bronchospasm, allergic reactions, rhinitis, epistaxis, back pain and arthralgias.
Estrogen replacement increases risk of thromboembolism and myocardial infarction, breast and endometrial cancer. Cholestatic jaundice, hypertriglyceridemia, pancreatitis may occur. Also, enlargement of uterine fibroids, migraines, edema.

Prognosis

Bisphosphonates and raloxifene can reverse progressive osteopenia and osteoporosis and can decrease fracture risk. Give calcium supplements with meals to reduce risk of calcium oxalate nephrolithiasis. Bone pain reduction may be noted within 2–4 weeks on nasal calcitonin.