Osteoporosis, the disease of the bone that afflicted King David of Israel 3000 years ago1, is no longer considered a consequence of aging. It is increasingly being recognized as a major health care concern, and accounts for more than 1.5 million fractures annually in the United States.2
Bone loss that increases the risk of fractures can affect males and females of any age and ethnicty.3 This risk is recognized in patients with advanced Chronic Obstructive Pulmonary Disease4 and chronic liver diseases5, certain adolescents and patients who take specific medications may also be at risk.6
Osteoporosis is usually asymptomatic until a fracture occurs, family physicians must identify the appropriate timing and methods for screening those with subclinical osteoporosis and know when to implement preventive strategies.
The WHO definition of osteoporosis is based on measurement of bone mineral density (BMD) defined as a BMD of >2.5 standard deviations (SD) below the mean for young adults, while osteopenia is defined as a BMD between 1 and 2.5 SDs below the means for young adults (ie, the T score).7,8 The risk of fracture increasing to threefold for each SD decrease in BMD.9
Primary osteoporosis is classified into two major types, postmenopausal and senile. Postmenopausal osteoporosis manifests approximately 10 years after menopause. Loss of the trabecular bone is more, leading to vertebral crush fracture and Colles' fracture of the distal forearm. There may also be acute or chronic back pain, kyphosis and loss of height.10 Senile osteoporosis presents after the age of 70 years in both sexes, where there is a loss of both trabecular and cortical bone, and increased risk of hip and vertebral fractures.10
Secondary osteoporosis results from chronic conditions that leads to accelerated bone loss.(Table 1)11, and is a complication of long-term glucocorticoid therapy12 and chronic liver diseases.13
Bone mass reaches the peak in the third decade and then declines in both sexes, in women accelerating after the menopause13,14, low bone mass (osteopenia) predisposes to osteoporosis, which decreases the total amount of bone tissue, but the composition remains normal.10
Maintaining bone mass involves the activation of precursor osteoclasts, which erode individual remodeling sites (called basic multicellular units)15, stimulating the activation of osteoblast precursors, which refill each unit. In normal, young adult bone, phases in this activation-resorption-formation process are tightly coupled. Uncoupling of the resorptive and formation phases leads to bone loss. Numerous hormones, growth factors, including cytokines influence remodeling in the bone microenvironment.15 Contributing factors to osteoporosis include smoking16 and others (Table 2).
Pharmacological management of osteoporosis
includes the use of calcium and Vitamin D, Hormone Replacement Therapy (HRT), Calcitonin, Bisphosphonates and Selective Estrogen Receptor Modulator. Calcium and vitamin D alone are shown to be insufficient to prevent the bone loss, in addition urinary calcium excretion should be monitored for hypercalciuria.31 Hormone Replacement Therapy (HRT) is advocated to prevent osteoporosis in postmenopausal women.32 Randomized trial data supporting HRT impact on fracture is limited. A large randomized controlled trial failed to demonstrate a beneficial effect of HRT on secondary prevention of cardiovascular risk and that HRT may have associated risks of breast and endometrial cancer and increase the risk of thromboembolism.33 Testosterone in men with low testosterone levels have shown to improve muscle mass and strength.34, 35
Selective estrogen receptor modulator such as raloxifene have estrogen like effects on the bone without the risk of breast or endometrial cancer.36 Raloxifene inhibits trabecular and vertebral bone loss by blocking the activity of cytokines, which stimulate bone resorption. A meta-analysis of raloxifene on bone density demonstrated that it increases bone density and has positive impact on verteberal fractures.37
Calcitonin has shown to prevent trabecular bone loss during the first few years of menopause. Meta-Analysis of Calcitonin on bone density demonstrates increase in bone density and likelihood of reducing the risk of vertebral fracture; its effect on non-vertebral fracture remains uncertain.38
Bisphosphonates as oral alendronate, cyclical etidronate, clodronate, risedronate and intravenous zoledronic acid have shown to increase BMD and a trend towards decreasing vertebral fractures39 and preventing corticosteroid induced osteoporosis in primary biliary cirrhosis5 and chronic lung disease.40 A Meta-Analysis study on Alendronate clearly demonstrate that it increases bone density in both early postmenopausal women and those with established osteoporosis while reducing the rate of vertebral fractures over 2-3 years of treatment.41 Risedronate substantially reduces the risk of both vertebral and non-vertebral fractures and increase bone density in both early postmenopausal and those with established osteoporosis.42
Annual infusion of zoledronic acid has shown to be an effective treatment for osteoporosis.43
Treatment is recommended in postmenopausal women with T scores of < -2 or < -1.5 with one risk factor, and men with T scores of < -2.5.46-48
1. Noun B, Louba L. What was the disease of the bone that affected King David.J Gerontology 2002;57:M152-4.
2. Ray NF, Chan JK, Thamer M, et al. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res1997;12:24-35.
3. Kanis JA, Johnell O, Oden A, et al. Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis. Bone 2000;27:585-90.
4. Biskobing DM. COPD and osteoporosis. Chest 2002;121:609-10.
5. Compston J. The effect of liver disease on bone. In: McIntyre, Benhamou JP, Bircher J, et al. (ed). Oxford textbook of hepatology. Oxford: University Press, 1991.
6. Toogood JH, Baskerville JC, Markov AE, et al. Bone mineral density and the risk of fracture in patients receiving long-term inhaled steroid therapy for asthma. J Allergy Clin Immunol1995;96:157-66.
7. Estell R. Treatment of postmenopausal osteoporosis. N Engl J Med 1998; 338:736-46.
8. World Health Organization. Study group on assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva: WHO 1994.
9. Marshall D, Jonhell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312:1254-9.
10. Jack SD. Mineral and Metabolic Bone Disease. Washington Manual of Medical Therapeutics. 1998. 29th ed.Philadelphia: Lippincot - Raven 1998, pp. 450-51.
11. Harper KD, Weber TJ. Secondary osteoporosis: diagnostic considerations. Endocrinol Metab Clin North Am 1998;27:325-48.
12. Goldstein MF, Fallon JJ, Harning R. Chronic glucocorticoid therapy-induced osteoporosis in patients with obstructive lung disease. Chest.,1999;116: 1733-49.
13. Collier JD, Ninkovic M, Compston JE. Guidelines on the management of osteoporosis associated with chronic liver disease. Gut 2002;50:11-19.
14. Tresolni CP, Gold DT, Lee LS (eds). Working with patents to prevent, treat and manage osteoporosis: a curriculum guide for health professionals. 2nd ed.San Francisco: National Fund for Medical Education, 1998.
15. Heaney RP. Pathophysiology of osteoporosis. Endocrinol Metab Clin North Am 1998;27:255-65.
16. Daniel HW. Osteoporosis of the slender smoker. Arch Intern Med 1976;136:298-304.
17. Taxel P. Osteoporosis: detection, prevention and treatment in primary care. Geriatrics 1998;53:22-33.
18. National Osteoporotic Foundation, 1996 and 2015 osteoporosis prevalence figures: state-by-state report. January 1997. Women's Health Matters 1998;2:1.
19. Pakistan Medical Research Council. National Health Survey of Pakistan. Islamabad: PMRC 1998.
20. Habiba U, Ahmad S, Hassan L. Predisposition to osteoporosis in postmenopausal women. J Coll Physicians Surg Pak 2002;12:297-301.
21. Kroger H, Reeve J. Diagnosis of osteoporosis in clinical practice. Ann Med 1998;30:278-87.
22. Blake GM, Fogelman I. Applications of bone densitometry for osteoporosis. Endocrinol Metab Clin North Am 1998;27:267-88.
23. U.S Preventive Services Task Force. Guide to clinical preventive services. 2nd ed. Baltimore: Williams and Wilkins, 1996, pp. 1-28.
24. National Osteoporosis Foundation. Physician's guide to prevention and treatment of osteoporosis. Washington, D.C: the Foundation, 1998, pp. 1-2.
25. Reid IR. The role of calcium and vitamin D in the prevention of osteoporosis. Endocrinol Metab Clin North Am 1998;27:389-98.
26. Pasco JA, Kotowicz MA, Henry M, et al. Statin Use, BMD and fracture risk: GEELONG osteoporosis study. Arch Intern Med 2002;162:537-40.
27. Dalsky GP, Stocke KS, Ehsani AA, et al. Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women. Ann Intern Med 1988;108:824-28.
28. Henderson NK, White CP, Eisman JA. The role of exercise and fall risk reduction in the prevention of osteoporosis. Endocrinol Metab Clin North Am 1998;27:369-87.
29. Bourjeily G, Rochester CL. Exercise training in chronic obstructive pulmonary disease. Clin Chest Med 2000;21:763-81.
30. McClung MR, Spencer K. Non-pharmacological therapy for osteoporosis. In: Rosen CJ, (ed.) Osteoporosis: diagnosis and therapeutic principles. Totowa, NJ: Humana Press 1996, pp.189-99.
31. Sambrook P, Birmingham J, Kelly P, et al. Prevention of corticosteroid osteoporosis: a comparison of calcium, calcitriol, and calcitonin. N Engl J Med 1993;328:1747-52.
32. Altkorn D, Vokes T. Treatment of postmenopausal osteoporosis.JAMA 2001;285:1415-18.
33. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/Progestin Replacement Study (HERS) Research Group. JAMA 1998;280:605-13.
34. Orwoll ES. Osteoporosis in men. Endocrinol Metab Clin North Am 1998; 27:349-67.
35. Snyder PJ, Peachey H, Berlin JA, et al. Effects of testosterone replacement in hypogonodal men. J Clin Endocrinl Metab 2000;85:2670-7.
36. Clemett D, Spender CM. Raloxifene: a review of its use in postmenopausal osteoporosis. Drugs 2000;60:379-411.
37. Cranney A, Tugwell P, Zytaruk N, et al. Meta-analysis of Raloxifene for the Prevention and treatment of postmenopausal osteoprosis. Endocr Rev 2002;23:524-28.
38. CranneyA, Tugwell P, Zytaruk N, et al.. Meta-analysis of calcitonin for the treatment of postmenopausal osteoprosis. Endocr Rev 2002;23:540-51.
39. National Osteoporosis Foundation. Physician's guide to prevention and treatment of osteoporosis. Washington, D.C: the Foundation 1998, pp.1-2.
40. Wang WQ, Ip MS, Tsang KW, et al. Antiresorptive therapy in asthmatic patients receiving high dose inhaled steroids: a prospective study for 18 months. J Allergy Clin Immunol 1998;101:445-50.
41. Cranney A, Wells G, William A. Meta-analysis of therapies for postmenopausal osteoporosis. Endocr Rev 2002;23:508-16.
42. Cranney A, Tugwell P, Adachi J, et al. Meta-analysis of therapeutics for post-menopausal osteoporosis. Endocr Rev 2002;23:517-23.
43. Reid IR, Brown JP, Burckhardt P, et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 2002;346:653-61.
44. Reid IR.Therapy of osteoporosis: calcium, vitamin D, and exercise. Am J Med Sci 1996;312:278-86.
45. Task Force on osteoporosis guidelines. American College of Rheumatology. Arthritis Rheum 1996;39:1791-1801.
46. Altkorn D, Vokes T. Treatment of postmenopausal osteoporosis. JAMA 2001;285:1415-18.
47. Orwoll ES. Osteoporosis in men. Endocrinol Metab Clin North Am 1998;27:349-67.
48. Jeanette E. Evaluation and assessment of osteoporosis. Am Fam Physician 2001;63: 897-904.