You are in: eMedicine Specialties > Physical Medicine and Rehabilitation > MEDICAL DISEASES Osteoporosis (Primary)Article Last Updated: Dec 6, 2006AUTHOR AND EDITOR INFORMATIONAuthor: Srinivas R Nalamachu, MD, Clinical Asst Professor, Department of Internal Medicine, Mid America Physiatrists Srinivas R Nalamachu is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation Coauthor(s): Shireesha Nalamasu, MD, Consulting Staff, Methodist Hospital, Indianapolis; Hospitalist, Respiratory and Critical Care Consultants, PC Editors: Robert J Kaplan, MD, Associate Professor, Department of Physical Medicine and Rehabilitation, University of Kansas School of Medicine and Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Richard Salcido, MD, Chairman, Erdman Professor of Rehabilitation, Department of Physical Medicine and Rehabilitation, University of Pennsylvania School of Medicine; Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady of Lourdes Medical Center; Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers, Phoenix Author and Editor Disclosure Synonyms and related keywords: osteoporosis, metabolic bone disorder, metabolic bone disease, bone mass, bone density, osteopenia INTRODUCTIONBackgroundOsteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to bone fracture. PathophysiologyBone tissue undergoes constant remodeling. Under the physiologic conditions, bone formation and resorption are in a fair balance. After the third decade of life, bone resorption exceeds bone formation and leads to osteopenia and, in severe situations, osteoporosis. Women lose 30-40% of their cortical bone and 50% of their trabecular bone over their lifetime, as opposed to men who lose 15-20% of their cortical bone and 25-30% of trabecular bone. FrequencyUnited StatesAccording to the National Institutes of Health (NIH), more than 25 million people in the United States are affected by osteoporosis. Women make up 80% of the people affected by this disease. InternationalOsteoporosis is by far the most common metabolic bone disease in the world. Mortality/Morbidity
RaceCaucasians are at higher risk for osteoporosis than people of other races. SexWomen are at a significantly higher risk for osteoporosis. In primary osteoporosis, the female-to-male ratio is 5:1. AgeBone loss begins in the fourth decade of life. Bone loss is slow in the fourth decade, followed by a rapid loss in the fifth and sixth decades. CLINICALHistoryA complete medical history should be obtained, including the patient's age, medical problems, medications, family history of osteoporosis, information on menarche and menopause, smoking history, and any recent fractures.
PhysicalPhysical examination should focus on any loss of height, kyphosis, and the patient's overall stature. CausesRisk factors for osteoporosis include the following:
DIFFERENTIALSPaget Disease
|
| Drug Name | Estrogens-conjugated (Premarin) |
|---|---|
| Description | In the past, estrogen replacement was considered a primary therapy for prevention of postmenopausal osteoporosis. Estrogen had the additional advantages of controlling menopausal symptoms and presumptive prevention or delay of cardiovascular disease. However, data from the Women's Health Initiative (WHI) revealed that estrogen-progestin therapy does not reduce the risk of coronary heart disease and it increases the risk of breast cancer, stroke, and venous thromboembolic events. As a result of these findings, other antiresorptive agents are now the drugs of choice and are prescribed more frequently for prevention and treatment of osteoporosis in postmenopausal women. |
| Adult Dose | 0.3 mg/d PO on day 21 of 28-d cycle; add progestin on days 10-14 |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; pregnancy; thromboembolic disorders; breast and endometrial cancer; undiagnosed vaginal bleeding |
| Interactions | May reduce hypoprothrombinemic effect of anticoagulants; coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce estrogen levels; pharmacologic and toxicologic effects of corticosteroids may occur as a result of estrogen-induced inactivation of hepatic P450 enzyme; loss of seizure control noted when administered concurrently with hydantoins |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Caution in breastfeeding and impaired liver function; caution warranted in CAD (possible increase in coronary events in patients on hormonal therapy for osteoporosis) |
| Drug Name | Estradiol (Estrace, Vivelle, Climara, Estraderm, Esclim, Alora) |
|---|---|
| Description | Restores estrogen levels to concentrations that induce negative feedback at gonadotrophic regulatory centers; this, in turn, reduces release of gonadotropins from pituitary. Increases synthesis of DNA, RNA, and many proteins in target tissues. Inhibits osteoclastic activity and delays bone loss. Evidence also suggests a reduced incidence of fractures. |
| Adult Dose | Tab: 1-2 mg/d PO in cyclic regimen of q3wk on and 1 wk off Transdermal: Initiate with patch that releases at least 0.05 mg/d of estradiol, adjust dosage if necessary to control concurrent menopausal symptoms |
| Pediatric Dose | Not recommended |
| Contraindications | Documented hypersensitivity; thrombophlebitis, undiagnosed vaginal bleeding |
| Interactions | May reduce hypoprothrombinemic effects of anticoagulants; estrogen levels may be reduced with coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; corticosteroid levels may increase with concurrent ethinyl estradiol; use with hydantoins may cause spotting or breakthrough bleeding and pregnancy; increased fluid retention caused by estrogen intake may reduce seizure control |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Caution in hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease, CAD |
| Drug Name | Ethinyl estradiol and norethindrone (FemHRT) |
|---|---|
| Description | Used to treat moderate-to-severe vasomotor symptoms and to prevent osteoporosis associated with menopause. |
| Adult Dose | 1 tab PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity, endometrial, and hepatic cancer; thromboembolic disorders; undiagnosed vaginal bleeding; smokers >35 y; cardiovascular disease |
| Interactions | Phenobarbital, phenytoin, paramethadione, carbamazepine, troglitazone, rifampicin, and griseofulvin induce enzymes that decrease levels of contraceptive steroids; oral anticoagulants may increase thromboembolic potential |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease, CAD |
These inhibit osteoclastic bone resorption. Although no research data support the idea that use of intranasal calcitonin reduces the incidence of fractures, studies do show increase in bone density with the use of calcitonin.
| Drug Name | Calcitonin (Miacalcin, Osteocalcin injection) |
|---|---|
| Description | Lowers elevated serum calcium levels in patients with multiple myeloma, carcinoma, or primary hyperparathyroidism. Can expect a higher response when serum calcium levels are high. Now FDA approved for the treatment of osteoporosis. Administered intranasally. Onset of action approximately 2 h after injection, and activity lasts 6-8 h. May lower calcium levels for 5-8 d by about 9% if given q12h. IM route preferred at multiple injection sites with dose > 2 mL. |
| Adult Dose | 1 spray/d into alternate nostrils |
| Pediatric Dose | Not applicable |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Hypocalcemia; examine urine sediment during prolonged therapy |
These agents progressively reduce bone loss and increase bone mass.
| Drug Name | Alendronate sodium (Fosamax) |
|---|---|
| Description | Widely used first-line therapy for the treatment of osteoporosis. |
| Adult Dose | Prevention: 5 mg PO qd Postmenopausal: 10 mg PO qd |
| Pediatric Dose | Not approved |
| Contraindications | Documented hypersensitivity; hypocalcemia, abnormalities of the esophagus, inability to stand upright for 30 min |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in upper GI disease; must be taken at least 30 min before first food, beverage, or medication of the day and should be taken with large amounts of water; caution in renal impairment Monitor therapy if taking aminoglycosides, aspirin, or phosphate supplements Consider therapy modification if taking antacids, calcium salts, iron salts, magnesium salts, or NSAIDs |
| Drug Name | Risedronate (Actonel) |
|---|---|
| Description | Potent aminobisphosphonate. Inhibits bone resorption via actions on osteoclasts or osteoclast precursors. In a comparative study, normalization of alkaline phosphatase levels achieved in 77% of the patients treated with risedronate, compared with 10% with 400-mg etidronate. After 12 and 18 mo, 60% and 53% of patients treated with risedronate still had alkaline phosphatase levels in the reference range. Used in patients with GI side effects, with alendronate as first-line therapy. |
| Adult Dose | 5 mg PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity, hypocalcemia, or renal impairment |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor hypercalcemia-related parameters (eg, serum levels of calcium, phosphate, magnesium, potassium); maintain adequate intake of calcium and vitamin D to prevent severe hypocalcemia; caution in active upper GI problems; do not administer with alendronate for osteoporosis in postmenopausal women; adverse effects include diarrhea, headache, and arthralgia Monitor or modify therapy if taking antacids, calcium salts, or multivitamins with minerals Caution advised if taking aspirin/caffeine/CNS depressant combinations or aspirin/opiate combinations |
| Drug Name | Ibandronate (BONIVA) |
|---|---|
| Description | Inhibits osteoclast-mediated bone resorption. In postmenopausal women, reduces bone turnover rate, leading to a net gain in bone mass. |
| Adult Dose | 2.5 mg PO qd; administer with water at least 1 h prior to first food or beverages (other than water) of the day |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; uncorrected hypocalcemia; inability to stand or sit upright for at least 60 min following drug administration |
| Interactions | Multivalent cations (eg, calcium, aluminum, magnesium, iron) decrease absorption, administer ibandronate at least 1 h prior to vitamin and mineral supplements; NSAIDs may aggravate GI irritation |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May cause upper GI disorders (eg, dysphagia, esophagitis, ulceration), minimize GI risk by standing or sitting upright 1 h following dose; calcium and vitamin D supplementation required; not recommended with severe renal impairment (ie, CrCl <30 mL/min) |
These are antiresorptive agents, like estrogen. However, because of their selective receptor modulating property, they provide the beneficial effects of estrogens without the adverse effects.
| Drug Name | Raloxifene (Evista) |
|---|---|
| Description | Selective estrogen receptor modulator that decreases bone loss. FDA approved for treatment of osteoporosis. Used to prevent bone loss and reduce incidence of fractures. |
| Adult Dose | 60 mg PO qd; supplement with 400 U/d vitamin D |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; active thromboembolic disorder; pregnancy or planned pregnancy, and DVT or history of DVT, breastfeeding |
| Interactions | None reported |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Caution in history of venous thromboembolism, pulmonary embolism, cardiovascular disease, renal or hepatic insufficiency, concurrent use with estrogens, and history of cervical/uterine carcinoma |
These supplements are used to increase calcium levels.
| Drug Name | Calcium carbonate (Oystercal, Caltrate) |
|---|---|
| Description | Calcium supplementation in patients at young ages has been proven to lower the incidence of fractures. |
| Adult Dose | 1000-1500 mg PO qd in divided doses |
| Pediatric Dose | Not applicable |
| Contraindications | Renal calculi, hypercalcemia, hypophosphatemia, renal or cardiac disease, digitalis toxicity |
| Interactions | May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Hypercalcemia or hypercalcuria may occur with therapeutic amounts |
Parathyroid hormone promotes new bone formation, leading to increased bone mineral density. Teriparatide is a biologic product containing a portion of human parathyroid hormone, which primarily regulates calcium and phosphate metabolism in bones. Teriparatide is approved for men or women at high risk of fracture due to primary or hypogonadal osteoporosis or postmenopausal osteoporosis, respectively.
| Drug Name | Teriparatide (Forteo) |
|---|---|
| Description | Recombinant human parathyroid hormone rhPTH (1-34), which has a sequence identical to 34 N-terminal amino acids (biologically active region) of 84-amino acid human parathyroid hormone (PTH). Acts as endogenous PTH, regulating calcium and phosphate metabolism in bone and kidney. Works primarily to stimulate new bone by increasing number and activity of osteoblasts (bone-forming cells). Additional physiologic actions include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. When administered with calcium and vitamin D, teriparatide increases bone mineral density and decreases risk of fractures in patients with osteoporosis. |
| Adult Dose | 20 mcg SC qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; increased risk of osteosarcoma (Paget disease of bone or unexplained elevations of alkaline phosphatase levels, open epiphyses, or prior skeletal irradiation therapy); children or growing adults; patients with bone metastases or history of skeletal malignancies, and those with metabolic bone diseases other than osteoporosis |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor for hypercalcemia; may cause orthostatic hypotension (particularly after first several doses), dizziness, or leg cramps |
Osteoporosis (Primary) excerpt
Article Last Updated: Dec 6, 2006