by Michele F. Bellantoni, M.D
- Screening for Low Bone Mass and Bone Turnover
- Strategies for Management in a Primary Care Setting
- Management of Osteoporosis Fractures and Physical Frailty
Is it a Disease?
While the loss of bone mass is an expected part of aging, it has consequences for successful aging. The medical literature defines osteoporosis as a disease characterized by abnormalities in the amount and architectural arrangement of bone tissue that leads to impaired skeletal strength and an undue susceptibility to fractures(ref 1). The World Health Organization has proposed a clinical definition of osteoporosis based on epidemiological data that link low bone mass with increased fracture risk. In study populations of Caucasian postmenopausal women, a bone mineral density that was lower than 2.5 standard deviations (SD) of normal peak bone mass was associated with a fracture prevalence of 50&037;, meaning that 50% of women with bone mass at this level had at least one bone fracture(ref 2). Based on these data, the WHO defined osteoporosis as bone mineral density 2.5 or more SD below peak bone mass, osteopenia as bone mass between 1.0 and 2.5 SD below peak, and normal as 1.0 SD below normal peak bone mass or higher. However, the WHO criteria apply only to Caucasian, postmenopausal women, and not men, premenopausal women, or women of ethnicity other than Caucasian. We have yet to classify clinically significant low bone mass in this populations.
How common is osteoporosis?
Using the WHO criteria, 30% of Caucasian postmenopausal women in the US have osteoporosis, and 54% have osteopenia. The prevalence of low bone mass increases with age. Using the WHO definition of osteoporosis, the prevalence in the US of osteoporosis in Caucasian postmenopausal women based on the lowest bone mass at any site is estimated to be 14% of women aged 50-59 years, 22% of women aged 60-69 years, 39% women aged 70-79 years, and 70% women aged 80 years or greater(ref 3).
Factors Influencing Bone Mass
Peak bone mass occurs for both men and women by the early thirties. Genetic factors play the greatest role in determining peak bone mass, but there are clinically significant contributions from nutrition, drug exposures, endocrine health following puberty, and weight-bearing status (ref 4). For example, most teenagers and young adults do not receive the Recommended Daily Allowance (RDA) for calcium of 1200 mg. Smoking and excessive alcohol use contribute to low bone mass. Systemic glucocorticoid use of 7.5 mg daily or greater impairs bone formation. Phenytoin and other anti-seizure medications impair vitamin D metabolism. Oligomenorrhea and amenorrhea cause accelerated bone loss, as do hyperthyroidism or over-replacement of thyroxine supplementation such that the serum TSH is suppressed. Immobility is associated with thinning of the bone from lack of weight-bearing forces.
The menopausal transition is associated with bone loss that can exceed 4% per year and extend for 10 years or more(ref 4). There is individual variation as to the rate and duration of bone loss. It appears that body fat, a non-ovarian source of circulating estrogens, influences the rate of bone loss; with higher amounts of body fat protecting against menopausal bone loss. Studies of African American women have shown that although on average they have higher peak bone mass than Caucasian women, they experience comparable rates of menopausal bone loss that are clinically significant for lean African American women.
Bone loss in women continues into older age, as the Study of Osteoporotic Fractures showed clinically significant bone loss occurring in women 65 years of age and older (ref 5). Factors contributing to this bone loss include inadequate intake of calcium and vitamin D, lack of weight-bearing exercise, and possibly age-related changes in endocrine functions beyond those of estrogen deficiency.
On average, men achieve higher peak bone mass than women, and they do not experience as dramatic a change in reproductive function with aging as do menopausal women. However, levels of circulating testosterone as well as those of growth hormone and adrenal androgens decrease with normal healthy aging. These age-related endocrine changes combined with nutritional and lifestyle changes result in a gradual loss of bone mass with normal aging in men. Accelerated bone loss occurs with abrupt loss of testosterone production such as that experienced during the treatment of prostate cancer.
Does Bone Mass Predict Fracture Rate?
For every one standard deviation below peak bone mass the risk of vertebral fracture is two times that of normal bone mass, and for the hip, the risk is 2.5 times.(ref 6) Low bone mass is a modifiable risk factor for fracture analogous to hypercholesterolemia or hypertension for myocardial infarction and stroke.
The clinical consequence of low bone mass is fracture. Pain and immobility result from fractures of the limbs and spine. Multiple vertebral fractures result in irreversible spinal deformity and chronic pain syndromes. However, hip fractures result in institutionalization and excess mortality. One year mortality according to age at hip fracture are estimated to be roughly 20% in individuals less than age 70 years; 30% for ages 70-79.9 years, and almost 40% ages 80-89.9.(ref 7) In summary, bone loss is a natural consequence of aging that if untreated, results in loss of independence and quality of life. Yet, preventive and treatment strategies have been developed (see below), thus making bone health an appropriate part of preventive health care in the primary care setting.
Do Previous Fractures Predict Future Fractures?
One vertebral fracture is associated with a 5-fold increase in risk for subsequent vertebral fractures and a 2-fold increase in hip fracture. Two or more vertebral fractures increase the risk of subsequent vertebral fracture by 12-fold.(ref 8) In our experience, almost half of frail elders admitted to an inpatient rehabilitation unit following a fracture had experienced a previous fracture.(ref 9) The majority of the earlier fractures were of minimal or short-term impact on functional state; whereas the more recent fracture greatly impacted physical function. Yet, none of the earlier fractures resulted in an effective treatment program that may have prevented the more recent fracture.
Do Falls Increase Risk for Fracture?
The great majority of all fractures in older women result from falls.(ref 10) Fall risk factors include leg weakness, impaired gait, and balance dysfunction. These can occur from global physical deconditioning as well as specific syndromes such as stroke, osteoarthritis of selective joints, and medical conditions such as polypharmacy, use of psychoactive medications, and orthostasis.(ref 11)
The occurrence of fracture during a fall is determined by the intensity of the trauma and by bone strength. Risk factors identified for injurious falls include fear of falling, reduced knee extension strength, and poor distance visual acuity.(ref 12) A simple test that predicts risk of injurious falls is the one-leg balance test – the ability to stand unassisted for 5 seconds on one leg.(ref 13) Inability to perform this task increased relative risk of injurious falls by 2.1 (confidence intervals 1.04-4.3).
Resources of Patient Education
- National Osteoporosis Foundation – 1-800-223-9994
- National Institute on Aging – 1-800-222-2225
- Arthritis Foundation – 1-800-365-3811
- Consensus Development Conference: Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med94:646-650, 1993
- The WHO Study Group: Assessement of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva, World Health Organization, 1994.
- Melton LJ III. How many women have osteoporosis now? J Bone Miner Res 10:175-177, 1995.
- Bellantoni M. Osteoporosis and Other Metabolic Bone Diseases, ClinicalAspects of Aging, 5th edition, William Reichel, M.D., ed., Williams and Wilkins, Baltimore, MD, 1999.
- Cummings SR et al. Appendicular bone density and age predict hip fracture in women. JAMA 263:665-668, 1990.
- Melton LJ III et al. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 8:1227-1233, 1993.
- Miller PD. Management of osteoporosis. Advances in Internal Medicine 44:175-207, 1999.
- Ross PD et al. Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Annals of Int Med114:919-923, 1991.
- Humphrey K, Bellantoni MF, Remsburg R. Evaluation of a multidisciplinary care plan for the treatment of osteoporosis in the frail elderly. Abstract presented at the annual meeting of the American Geriatrics Society, Seattle, WA, May 1998.
- Cummings SR, Nevitt MC, for the Study of Osteoporotic fractures Research Group. Non-skeletal determinants of fractures: The potential importance of the mechanics of falls. Osteoporosis Int 1(suppl):657-670, 1994.
- Tinneti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 319:1701-1707, 1988.
- Luukinen H, Koski K, Laippala P, et al. Factors predicting fractures during failing impacts among home-dwelling older adults. J Am Geriatr Soc 45:1302-1309, 1997.
- Vellas B, Wayne S, Romero L, et al. One-leg balance is an important predictor of injurious falls in older persons.J Am Geriatr Soc 45:735-738, 1997.
- Cheng S, Tylavsky F, Carbone L. Utility of ultrasound to assess risk of fracture. J Am Geriatr Soc45(11):1392-1394, 1997.
- Ganero P, Hausherr E, Chapuy MC, et al. Markers of bone resorption predict hip fracture in elderly women: The EPIDOS prospective study. J Bone Miner Res 11:1531-1538, 1996.
- Health Care Financing Administration. Medic-are Program; Medicare coverage and payment for bone mass measurements. Federal Register June 24, 63(121):34320-34329, 1998.
- Miller PD, Bonnick SL, Rosen CJ. Consensus of an international panel on the clinical utility of bone mass measurements in the detection of low bone mass in the adult population. Calcif Tissue Int 58:207-214, 1998.
- Lydick E, Cook K, Turpin J, et al. Development and validation of a simple questionnaire to facilitate identification of women likely to have low bone density. Am J Man Care 4:37-48, 1998.
- Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med 338:736-746, 1998.
- Ensrud KE, Palermo L. Black DM, et al. Hip and calcaneal bone loss increase with advancing age: longitudinal results from the study of osteoporotic fractures. Journal of Bone and Mineral Research 10:1778-87, 1995.
- Schnitzer T, Bone HG, Crepaldi G, et al. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Aging Clin Exp Res 12:1-12, 2000.
- Rico H, et al. Total and regional bone mineral content and fracture rate in postmenopausal osteoporosis treated with salmon calcitonin. Calcif. Tiss. Int. 56:181-185, 1995.
- Reginster TY, Meurmans L, Zegels B, et al. The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. Ann Intern Med 129:1-8, 1998.
- Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. JAMA 282:1344-1352, 1999.
- Saag KG, Emkey R, Schnitzer TS, et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med 39:292-9, 1998.
- McClung M, Clemmesen B, Daifotis A, et al. Alendronate prevents postmenopausal bone loss in women without osteoporosis. Ann Intern Med 128:253-261, 1998.
- Bone HG, Greenspan SL, McKeever C, et al. Alendronate and estrogen effects in postmenopausal women with low bone mineral density. J Clin Endocrinol Metab 85:720-726, 2000.
- Thiebaud D, Burckhardt P, Melchior J, et al. Two years of effectiveness of intravenous pamidronate versus oral flouride in postmenopausal osteoporosis. Osteoporosis International 4:76-83, 1994.
- Thiebaud D, Burckhardt P, Kriegbaum H. Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis. Am J Med 103:298-307, 1997.
- Tinneti ME, Baker DI, McAvay G, et al. A multifactorial intervention to reduce the risk of falling among elderly people living in the community. N Engl J Med 331:921-927, 1994.
- Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 280&$058;605-613, 1998.
- Kritz-Silverstein D, Barrett-Connor E. Long-term postmenopausal hormone use, obesity, and fat distribution in older women. JAMA 275:46-49, 1996.
- Kawas C, Resnick S, Morrison A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: The Baltimore Longitudinal Study of Aging. Neurology 48:1517-1521, 1997.
- Shaywitz BA, Shaywitz Se. Estrogen and Alzheimer disease: plausible theory, negative clinical trial. JAMA283:1055-6, 2000.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 50:1047-59, 1997.
- Sellers TA, Mink PJ, Cerhan JR, et al. The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer. Ann InternMed 127:973-80, 1997.
- Walsh BW, Kuller LH, Wild RA, et al. Effects of raloxifene on serum lipids and coagulation factors in health postmenopausal women. JAMA 279:1445-1451, 1998.
- Breuer B, Wallenstein S, Anderson R. Effect of tamoxifen on bone fractures in older nursing home residents. J AM Geriatr Soc 46:968-972, 1998.
- Zuckerman JD. Hip fracture. N Engl J Med 334:1519-1525, 1996.
- Hoenig H, Nusbaum N, Brummel-Smith K. Geriatric rehabilitation: state of the art. J AM Geriatr Soc 45:1371-1381, 1997.
- Cameron ID, Lyle DM, Quine S. Cost effectiveness of accelerated rehabilitation after proximal femoral fracture.J Clin Epidemiol 47:1307-1313, 1994.