Osteoporosis

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Chapter 38 Osteoporosis

INTRODUCTION

Description: Osteoporosis is characterized by loss of bone mass (calcium) that puts the patient at risk for fracture with minimal trauma or during activities of daily living. This process disproportionately affects older women and results in significant morbidity and mortality. Estimates of medical costs are as high as $10 billion each year in the United States.
Prevalence: Of women older than age 75 years (not receiving estrogen replacement), 40% have spine, hip, or forearm fractures; 80% of hip fractures occur in this group.
Predominant Age: Postmenopausal.
Genetics: More common in some races (Caucasian/oriental, thought to be a function of peak bone mass).

ETIOLOGY AND PATHOGENESIS

Causes: Alcohol use/abuse, chronic illness, diabetes mellitus, estrogen loss, especially early menopause, excessive caffeine use, family history of osteoporosis, high parity, high protein intake, inactivity/sedentary lifestyle, inadequate vitamin D intake or sun exposure, low body weight, medical therapy (anticonvulsants, corticosteroids, excess thyroid hormone replacement, long-term heparin or tetracycline use, loop diuretics, chemotherapy), poor diet/inadequate calcium intake (<1000 mg/day), white race or Asian, radiation therapy, smoking.
Risk Factors: Menopause (without estrogen replacement), inactivity, presence of other causes as listed previously. (Women suffer roughly a 10-fold increase in the normal rate of bone loss for a period of about 10 years beginning with the loss of ovarian function. This results in an average lifetime loss of approximately 35% of cortical bone mass and 50% of the more metabolically active trabecular bone. By comparison, men lose only about two thirds this amount.)

CLINICAL CHARACTERISTICS

Signs and Symptoms

• Asymptomatic
• Spinal, hip, or forearm fractures (with or without pain, fractures should be suspected in idiopathic back pain in at-risk patients)
• Loss of height (up to 4 to 8 inches)
• Development of kyphoscoliosis (“dowager’s hump”)

DIAGNOSTIC APPROACH

Differential Diagnosis

• Metastatic tumor (breast)
• Paget disease (osteitis deformans)
• Multiple myeloma
• Unreported trauma (abuse, elder abuse)
• Cushing’ syndrome

Associated Conditions: Dyspareunia, vulvodynia, atrophic vulvitis, increased risk of cardiovascular disease, hot flashes and flushes, sleep disturbances, urinary incontinence, and others associated with hypoestrogenic states.

Workup and Evaluation

Laboratory: No evaluation specifically indicated.
Imaging: Dual-energy x-ray absorptiometry (DEXA) or quantitative computed tomography. Routine radiographic studies (e.g., chest radiograph) do not detect changes until almost 30% of bone has been lost (approximately equal to fracture threshold, 1 g/cm2).
Special Tests: Urinary tests for bone metabolites are investigational only.
Diagnostic Procedures: Radiographic assessment of bone mass.

Pathologic Findings

Loss of bone calcium, thinning of trabeculae, microfractures, macrofractures (spine, hips, forearms).

MANAGEMENT AND THERAPY

Nonpharmacologic

General Measures: Smoking cessation, alcohol and caffeine intake in moderation, weightbearing exercise, adequate dietary calcium or supplementation.
Specific Measures: Bisphosphonates, calcitonin (infrequently used, reserved for selected patients as a therapeutic agent, not as prevention), selective estrogen receptor modulators (SERMs). Estrogen replacement therapy (when indicated for other reasons) will provide protection but is no longer considered sufficient to justify risks, based on the results of the Women’s Health Initiative (WHI) study, although significant concerns about the methodologies of this study exist.
Diet: Adequate dietary intake of calcium (1000 to 1500 mg/day) and vitamin D (400 to 800 IU daily). (Supplementation of vitamin D beyond this dose is generally not warranted.)
Activity: Weightbearing exercise or exercise against resistance. Low-impact activities for those with established bone loss.
Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP048 (Preventing Osteoporosis), AP047 (The Menopause Years), AP045 (Exercise and Fitness), AP066 (Hormone Replacement Therapy).

Drug(s) of Choice

Bisphosphonates—alendronate sodium (Fosamax) 10 mg PO daily (must be taken on arising for the day, with a full glass of water, and nothing by mouth for 30 minutes), risedronate sodium (Actonel) 30 mg PO weekly, ibandronate sodium (Boniva) 150 mg PO monthly or 3 mg IM every 3 months. Zoledronic acid has recently been approved for once yearly intravenous therapy. (New agents under development include bazedoxifene, with and without a combined estrogen.)
Selective estrogen receptor modulators (also known as tissue selective estrogens). Many of these agents have bone activity and have been shown to protect or increase bone mass. For most, no current data show a reduction in fracture rate, but this is expected to be the case when studies of longer-term use become available.
Estrogen replacement therapy (with progesterone if indicated). See “Menopause” for dosage options. (Estrogen’s effect on bone protection appears to depend on obtaining a relatively normal [premenopausal] blood level [40 to 60 pg/mL] and is not affected by the route of therapy.)

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Contraindications: See “Menopause.” Alendronate is contraindicated in patients with esophageal stricture or difficulty swallowing, an inability to sit or stand for 30 to 60 minutes, and in nursing mothers.
Precautions: See “Menopause.” Patients must remain upright after the ingestion of bisphosphonates to avoid esophageal irritation. Long-term use may be associated with impaired mineralization; therefore, bisphosphonates should be given cyclically. (Infrequent cases of osteonecrosis of the jaw have been reported in bisphosphonate users.) Vitamin D should be used judiciously, if at all, because doses that increase calcium absorption are close to doses that result in bone resorption. If calcitonin is used, it must be given with adequate calcium intake to avoid secondary hyperparathyroidism.
Interactions: See “Menopause.” Calcium supplements and antacids may interfere with the absorption of some bisphosphonates and must be taken later in the day.

Alternative Drugs

Calcium supplements should be reserved for those with inadequate intake or a food intolerance that prevents achievement of sufficient dietary levels. Calcium carbonate provides the greatest percentage of elemental calcium, and calcium citrate is highly absorbable, making both acceptable supplements. When used, these should be taken in divided doses over the course of the day. Excessive intake of calcium supplements has been associated with an increased risk of stone formation and should be discouraged.

FOLLOW-UP

Patient Monitoring: Normal health maintenance and continued (lifelong) compliance with medical therapy must be encouraged. Periodic measurement of height may detect asymptomatic spinal fractures.
Prevention/Avoidance: Estrogen replacement therapy at menopause (when otherwise indicated), good diet (adequate calcium and vitamin D intake), and exercise (weightbearing and otherwise). Elimination or reduction of bone toxins (smoking and excess alcohol consumption).
Possible Complications: After hip fracture, half of patients require assistance walking and 15% to 30% are institutionalized, often for the rest of their lives. Roughly, one of five patients with a hip fracture dies within 6 months of the fracture. Fracture of the hip is the twelfth leading cause of death for women.
Expected Outcome: The rate of bone loss may be slowed by medical interventions, but these are most successful if instituted early. Estrogen replacement (when started early) is associated with a reduction by about 50% in the rate of hip and arm fractures in postmenopausal women. This value has been reported to increase to more than 90% when estrogen is used for more than 5 years. Vertebral fractures may be reduced by as much as 80% for these same women.

MISCELLANEOUS

Pregnancy Considerations: No effect on pregnancy (generally not a consideration). Most bisphosphonates are pregnancy category C medications.
ICD-9-CM Codes: 733.01 (Postmenopausal).

REFERENCES

Level I

Black DM, Delmas PD, Eastell R, et alHORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809.

Goss AN. Bisphosphonate-associated osteonecrosis of the jaws. Climacteric. 2007;10:5.

Reid IR, Mason B, Horne A, et al. Randomized controlled trial of calcium in healthy older women. Am J Med. 2006;119:777.

Level II

Boonen S. Bisphosphonate efficacy and clinical trials for postmenopausal osteoporosis: similarities and differences. Bone. 2007;40:S26.

Chesnut CH. Treating osteoporosis with bisphosphonates and addressing adherence: a review of oral ibandronate. Drugs. 2006;66:1351.

Level III

American College of Obstetricians and Gynecologists. Osteoporosis. ACOG Practice Bulletin 50. Washington, DC: ACOG, 2004.

American College of Obstetricians and Gynecologists. Selective estrogen receptor modulators. ACOG Practice Bulletin 39. Washington, DC: ACOG, 2002.

Benhamou CL. Effects of osteoporosis medications on bone quality. Joint Bone Spine. 2007;74:39. Epub 2006 Nov 28

Clunie G. Update on postmenopausal osteoporosis management. Clin Med. 2007;7:48.

Dennison E, Mohamed MA, Cooper C. Epidemiology of osteoporosis. Rheum Dis Clin North Am. 2006;32:617.

Derk CT. Osteoporosis in premenopause. When are screening and treatment prudent? Postgrad Med. 2006;119:8.

Gass M, Dawson-Hughes B. Preventing osteoporosis-related fractures: an overview. Am J Med. 2006;119:S3.

Hadjidakis DJ, Androulakis II. Bone remodeling. Ann N Y Acad Sci. 2006;1092:385.

Hosking D, Chilvers CED, Christiansen C, et al. Prevention of bone loss with alendronate in postmenopausal women. N Engl J Med. 1998;338:485.

Kim DH, Vaccaro AR. Osteoporotic compression fractures of the spine; current options and considerations for treatment. Spine J. 2006;6:479.

Lambrinoudaki I, Christodoulakos G, Botsis D. Bisphosphonates. Ann N Y Acad Sci. 2006;1092:397.

Liberman UA. Long-term safety of bisphosphonate therapy for osteoporosis: a review of the evidence. Drugs Aging. 2006;23:289.

Llorens R. A review of osteoporosis: diagnosis and treatment. Mo Med. 2006;103:612.

Lobo RA. Menopause. In: Katz VL, Lentz GM, Lobo RA, Gershenson DM, editors. Comprehensive Gynecology. 5th ed. Philadelphia: Mosby/Elsevier; 2007:1050.

Mauck KF, Clarke BL. Diagnosis, screening, prevention, and treatment of osteoporosis. Mayo Clin Proc. 2006;81:662.

McCarus DC. Fracture prevention in postmenopausal osteoporosis: a review of treatment options. Obstet Gynecol Surv. 2006;61:39.

Miller RG. Osteoporosis in postmenopausal women. Therapy options across a wide range of risk for fracture. Geriatrics. 2006;61:24.

Mosekilde L, Vestergaard P, Langdahl B. Fracture prevention in postmenopausal women. Clin Evid. 2006;15:1543.

Poole KE, Compston JE. Osteoporosis and its management. BMJ. 2006;333:1251.

Pyon EY. Once-monthly ibandronate for postmenopausal osteoporosis: review of a new dosing regimen. Clin Ther. 2006;28:475.

Raisz LG. Clinical practice. Screening for osteoporosis. N Engl J Med. 2005;353:164.

Reid DM. Once-monthly dosing: an effective step forward. Bone. 2006;38:S18. Epub 2006 Mar 13.

Riggs BL, Melton LJIII. Medical progress: involutional osteoporosis. N Engl J Med. 1986;314:1676.

Rizer MK. Osteoporosis. Prim Care. 2006;33:943. vii.

Rosen CJ. Clinical practice. Postmenopausal osteoporosis. N Engl J Med. 2005;353:595.

Sambrook P, Cooper C. Osteoporosis. Lancet. 2006;367:2010.

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