- Email: [email protected]
Osteoporosis Detection and Treatment
Journal of Clinical Densitometry, vol. 2, no. 2, 105–107, Spring 1999 © Copyright 1999 by Humana Press Inc. All rights of any nature whatsoever reserved. 0169-4194/99/2:105–107/$10.75
Editorial
Osteoporosis Detection and Treatment Richard L. Prince, MD
sis? It is this, any program that does not have fracture detection as its end point misses the principal issue that most people are interested in. Thus, it would be more useful to compare the efficacy of a questionnaire to detect fracture with bone density testing to detect fracture rather than to study the efficacy of a questionnaire to detect low bone density. There have been remarkably few studies that have adopted the former approach because it is a much more difficult study design. If we are to undertake programs to detect highrisk individuals, when is the best time to start? It depends a lot on the efficacy, safety, and cost with which we can detect individuals at risk and on the safety and efficacy and cost of the treatments we offer them. Thus, the first question to be answered when considering a fracture prevention program is “What is the age-specific fracture rate?” If the actual rate of preventable fractures is low, there is little reason to devise a program to prevent them. Alternatively under these circumstances it is necessary for a detection program to utilize a method that has high sensitivity and specificity to detect an increased risk of fracture in the population selected for screening, that is, it must detect a high gradient of risk. Fracture data on premenopausal women are quite variable with rates varying from 1.7% per 5 yr in the UK (2) to 4.5% per 5 yr in Finland (3). Are these rates too low to warrant introduction of bone density testing and treatment programs for the whole population? Currently the answer is yes, especially as there are no data on the effectiveness of bone density testing to detect increased fracture risk in this population and no data on effective interventions to prevent fracture. Alternative strategies could be considered. These could include bone density and
In this edition of the Journal of Clinical Densitometry Jones and Scott (1) address the important issue of osteoporosis detection and treatment. They examine the efficacy of a questionnaire approach to detect premenopausal women with low femoral neck or lumbar spine as defined by a T score of –1 or less. They then go on to examine whether education of women at risk altered their behavior. The study design raises important questions of how we should be developing programs to prevent osteoporosis, in particular, the gold standard by which to evaluate these programs. In addressing this issue we first of all need to define what it is that we wish to prevent and why. Generally, our patients wish to live as long as possible as well as possible. Thus, they are principally concerned about the propensity of fracture to reduce their life expectancy and also to render them symptomatic. Symptoms occurring as a result of fracture include pain, deformity, and disability consequent on fracture and also the fear of developing these symptoms. Third part payers are interested in osteoporotic fracture because they have to pay for the consequences of the fracture. In view of the fact that hospitalization and long-term institutional care are the most costly aspects, it is these aspects that are of most interest to them. These considerations indicate that it is likely that most people are primarily interested in fracture prevention. They are only concerned about bone density because they have been informed that low bone density increases their probability of fracture with its significant consequences. What has this to do with the detection of osteoporoAddress correspondence to Richard L. Prince, M.D., University of Western Australia, Sir Charles Gairdner Hospital, Perth, W.A. 6009, Australia. E-mail: [email protected]
105
106 treatment programs targeted to subjects with historical risk factors. However, the etiological factors predisposing to fracture are site specific (3). Thus, in this age group risk factors for wrist fracture differ from risk factors for ankle fracture. Nevertheless, risk factors such as long-term prednisone use may be powerful enough to predict fracture even in this lowrisk population (4) Another approach to the problem of fracture prevention in premenopausal women is a whole population public health education strategy. In this regard Jones and Scott point out that the discovery of low bone density can lead to behavioral alteration, at least in the short term (1). However, if the aim is behavioral alteration, a surrogate outcome, it may be possible to achieve the same aim at lower cost by a more focused education campaign without bone density testing. It may be that in women before menopause selection of high-risk subjects using historical risk factors with or without bone density testing will be the most effective method of detecting women to target advice to change behavior with the aim of reducing the risk of fracture. Proving that such a program would actually prevent fracture is a daunting clinical research prospect. For example, if access to appropriate education is a human right, then it may be unethical to undertake a study that would involve withholding information to one study group. Nevertheless, if we are to stem the tide of disability and death associated with osteoporotic fracture, we should be prepared to examine prevention programs at all points in the pathogenesis and be prepared to study education techniques as well as pharmacological interventions. What about older patients? Here there are more data. If we are interested in the potentially preventable age-specific fracture rate, which categories of fracture are we interested in? It has been suggested that only low trauma fractures should be considered potentially preventable. However, recent data suggest that high trauma fractures are also associated with low bone mass (5). Should we include all fractures as potentially preventable including relatively insignificant fractures like those of toes and fingers or concentrate only on the classic osteoporotic fractures of the spine, hip, and wrist? In view of the fact that fractures of the face and finger have not been associated with low bone
Journal of Clinical Densitometry
Prince mass, perhaps they should be excluded (6). The inclusion or exclusion of fractures at particular sites obviously has a significant effect on the relevant rate of fracture. Differences in classification and ascertainment may in part explain differences in the age-specific, potentially preventable fracture rates for different populations. For example, the Study of Osteoporotic Fracture population rate for all fractures was 17% per 5 yr in 65 year olds and 25% per 5 yr in 80 year olds (6,7). However, if fractures other than hip, spine, and forearm are excluded, the rates were only 5.4% per 5 yr in 65 year olds and 12% per 5 yr in 80 year olds. Cross-sectional data from the UK using hospital outpatient and in-patient rates gives much lower rates of all fractures. In a 65 yr old it is about 6.5% per 5 yr and in an 80 year old it is about 18.4% per 5 yr (2,8). Australian all fracture rates are 13.9% per 5 yr in 65 yr olds and 46% per 5 yr in 80 yr olds (9). It has been argued on a cost-effectiveness grounds that bone density testing should be offered to otherwise healthy women after the age of 60 (7). At face value this seems reasonable in that the fracture rate over 5 yr in this age group is high irrespective of the population that has been studied. Secondly, bone density testing has been shown to detect individuals at high risk of fracture in this age group (10, 11). Finally, there is evidence from a large trial that targeting treatment at individuals with osteoporosis (T score –2.5) but not osteopenia (T score –1.6) reduces fracture rates at many sites with acceptable safety (12). Another method of selecting women for treatment involves the use of historical risk factors such as low body weight, previous fractures, and corticosteroid use with or without bone densitometery. This approach is often supported by third part payers by allowing bone densitometery rebates in subjects with the risk factors. For example, there is good evidence that previous vertebral and appendicular fracture predisposes to future vertebral fracture (13,14). The relative advantages of selective bone density testing using risk factors such as previous fracture compared to nonselective bone density testing in detecting high-risk subjects suggests an advantage from the combined approach. Furthermore, there are treatments of proven efficacy in reducing fractures in patients selected using a bone density and prevalent fracture strategy (15).
Volume 2, 1999
Osteoporosis Detection and Treatment Finally, a whole population intervention strategy could be undertaken without trying to detect highrisk individuals. In view of the very high rates of fracture in elderly subjects irrespective of the precise population or classification of fracture used, it would seem reasonable to target this group for a public health strategy. In view of good randomized controlled trial evidence of efficacy for calcium and vitamin D treatment in appendicular fracture prevention in countries in northern latitudes, these interventions should be seriously considered for a whole population intervention (16,17). However, long-term compliance with calcium supplementation is poor (18). Thus, careful consideration of methods of introducing these treatments should be undertaken, for example, by a food fortification approach. It is clear that achieving effective fracture prevention will require a variety of interventions targeted to particular age and risk groups. The availability of technology for early detection of fracture propensity coupled with effective treatments suggests that we should, in the near future, be able to significantly reduce age-specific fracture rates.
107
6.
7.
8.
9.
10. 11.
12.
13.
References 1. Jones G, Scott FS. 1999. Low bone mass in premenopausal parous women: identification and the effect of an information and bone density feedback program. J Clin Densitometry 2:109–115. 2. Donaldson LJ, Cook A, Thomson RG. 1990. Incidence of fractures in a geographically defined population. J Epidemiol Community Health 44:241–245. 3. Honkanen R, Tuppurainen M, Kroger H, Alhava E, Saarikoski S. 1998. Relationships between risk factors and fractures differ by type of fracture: a population based study of 12192 perimenopausal women. Osteoporosis Int 8:25–31. 4. Adinoff AD, Hollister JR. 1983. Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med 309:265–308. 5. Sanders KM, Pasco JA, Ugoni AM, Nicholson GC, Seeman E, Martin TJ, et al. 1998. The exclusion of high trauma fractures may underestimate the prevalence of bone fragility
Journal of Clinical Densitometry
14.
15.
16.
17.
18.
fractures in the community: the Geelong Osteoporosis Study. J Bone Miner Res 13:1337–1342. Seeley DG, Browner WS, Nevitt MC, Genant HK, Scott JC, Cummings SR. 1991. Which fractures are associated with low appendicular bone mass in elderly women? Ann. Intern Med 115:837–842. Eddy DM, Johnston CC, Cummings SR, Dawson-Hughes B, Lindsay R, Melton LJIII, et al. 1998. Osteoporosis: review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Osteoporosis Int 8:S7–S80. Knowelden J, Buhr AJ, Dunbar O. 1964. Incidence of fractures in persons over 35 years of age. Br J Prev Soc Med 18:130–141. Jones G, Nguyen T, Sambrook PN, Kelly PJ, Gilbert C, Eisman JA. 1994. Symptomatic fracture incidence in elderly men and women: the Dubbo osteoporosis epidemiology study (DOES). Osteoporosis Int 4:277–282. Johnston CC, Slemenda CW, Melton LJ, 1991. Clinical use of bone densitometry. N Engl J Med 324:1105–1109. Nevitt MC, Johnell O, Black DM, Ensrud K, Genant HK, Cummings SR. 1994. Bone mineral density predicts nonspine fractures in very elderly women. Osteoporosis Int 4:325–331. Cummings SR. 1998. Effect of alendronateon risk of fracture in women with low bone density but without vertebral fracture: Results from the Fracture Intervention Trial. JAMA 280:2077–2082. Wasnich RD, Davis JW, Ross PD. 1994. Spine fracture risk is predicted by non-spine fractures. Osteoporosis Int 4:1–5. Ross PD, Davis JW, Epstein RS, Wasnich RD. 1991. Preexisting fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med 114:919–923. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. 1996. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541. Dawson-Hughes B, Harris SS, Khall EA, Dallal GE. 1997. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 337:670–676. Chapuy MC, Arlot MF, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. 1992. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 327:1637–1642. Devine A, Prince RL, Bell R. 1996. Nutritional effect of calcium supplementation by skim milk powder or calcium tablets on total nutrient intake in postmenopausal women. Am J Clin Nutr 64:731–737.
Volume 2, 1999
Editorial
Osteoporosis Detection and Treatment Richard L. Prince, MD
sis? It is this, any program that does not have fracture detection as its end point misses the principal issue that most people are interested in. Thus, it would be more useful to compare the efficacy of a questionnaire to detect fracture with bone density testing to detect fracture rather than to study the efficacy of a questionnaire to detect low bone density. There have been remarkably few studies that have adopted the former approach because it is a much more difficult study design. If we are to undertake programs to detect highrisk individuals, when is the best time to start? It depends a lot on the efficacy, safety, and cost with which we can detect individuals at risk and on the safety and efficacy and cost of the treatments we offer them. Thus, the first question to be answered when considering a fracture prevention program is “What is the age-specific fracture rate?” If the actual rate of preventable fractures is low, there is little reason to devise a program to prevent them. Alternatively under these circumstances it is necessary for a detection program to utilize a method that has high sensitivity and specificity to detect an increased risk of fracture in the population selected for screening, that is, it must detect a high gradient of risk. Fracture data on premenopausal women are quite variable with rates varying from 1.7% per 5 yr in the UK (2) to 4.5% per 5 yr in Finland (3). Are these rates too low to warrant introduction of bone density testing and treatment programs for the whole population? Currently the answer is yes, especially as there are no data on the effectiveness of bone density testing to detect increased fracture risk in this population and no data on effective interventions to prevent fracture. Alternative strategies could be considered. These could include bone density and
In this edition of the Journal of Clinical Densitometry Jones and Scott (1) address the important issue of osteoporosis detection and treatment. They examine the efficacy of a questionnaire approach to detect premenopausal women with low femoral neck or lumbar spine as defined by a T score of –1 or less. They then go on to examine whether education of women at risk altered their behavior. The study design raises important questions of how we should be developing programs to prevent osteoporosis, in particular, the gold standard by which to evaluate these programs. In addressing this issue we first of all need to define what it is that we wish to prevent and why. Generally, our patients wish to live as long as possible as well as possible. Thus, they are principally concerned about the propensity of fracture to reduce their life expectancy and also to render them symptomatic. Symptoms occurring as a result of fracture include pain, deformity, and disability consequent on fracture and also the fear of developing these symptoms. Third part payers are interested in osteoporotic fracture because they have to pay for the consequences of the fracture. In view of the fact that hospitalization and long-term institutional care are the most costly aspects, it is these aspects that are of most interest to them. These considerations indicate that it is likely that most people are primarily interested in fracture prevention. They are only concerned about bone density because they have been informed that low bone density increases their probability of fracture with its significant consequences. What has this to do with the detection of osteoporoAddress correspondence to Richard L. Prince, M.D., University of Western Australia, Sir Charles Gairdner Hospital, Perth, W.A. 6009, Australia. E-mail: [email protected]
105
106 treatment programs targeted to subjects with historical risk factors. However, the etiological factors predisposing to fracture are site specific (3). Thus, in this age group risk factors for wrist fracture differ from risk factors for ankle fracture. Nevertheless, risk factors such as long-term prednisone use may be powerful enough to predict fracture even in this lowrisk population (4) Another approach to the problem of fracture prevention in premenopausal women is a whole population public health education strategy. In this regard Jones and Scott point out that the discovery of low bone density can lead to behavioral alteration, at least in the short term (1). However, if the aim is behavioral alteration, a surrogate outcome, it may be possible to achieve the same aim at lower cost by a more focused education campaign without bone density testing. It may be that in women before menopause selection of high-risk subjects using historical risk factors with or without bone density testing will be the most effective method of detecting women to target advice to change behavior with the aim of reducing the risk of fracture. Proving that such a program would actually prevent fracture is a daunting clinical research prospect. For example, if access to appropriate education is a human right, then it may be unethical to undertake a study that would involve withholding information to one study group. Nevertheless, if we are to stem the tide of disability and death associated with osteoporotic fracture, we should be prepared to examine prevention programs at all points in the pathogenesis and be prepared to study education techniques as well as pharmacological interventions. What about older patients? Here there are more data. If we are interested in the potentially preventable age-specific fracture rate, which categories of fracture are we interested in? It has been suggested that only low trauma fractures should be considered potentially preventable. However, recent data suggest that high trauma fractures are also associated with low bone mass (5). Should we include all fractures as potentially preventable including relatively insignificant fractures like those of toes and fingers or concentrate only on the classic osteoporotic fractures of the spine, hip, and wrist? In view of the fact that fractures of the face and finger have not been associated with low bone
Journal of Clinical Densitometry
Prince mass, perhaps they should be excluded (6). The inclusion or exclusion of fractures at particular sites obviously has a significant effect on the relevant rate of fracture. Differences in classification and ascertainment may in part explain differences in the age-specific, potentially preventable fracture rates for different populations. For example, the Study of Osteoporotic Fracture population rate for all fractures was 17% per 5 yr in 65 year olds and 25% per 5 yr in 80 year olds (6,7). However, if fractures other than hip, spine, and forearm are excluded, the rates were only 5.4% per 5 yr in 65 year olds and 12% per 5 yr in 80 year olds. Cross-sectional data from the UK using hospital outpatient and in-patient rates gives much lower rates of all fractures. In a 65 yr old it is about 6.5% per 5 yr and in an 80 year old it is about 18.4% per 5 yr (2,8). Australian all fracture rates are 13.9% per 5 yr in 65 yr olds and 46% per 5 yr in 80 yr olds (9). It has been argued on a cost-effectiveness grounds that bone density testing should be offered to otherwise healthy women after the age of 60 (7). At face value this seems reasonable in that the fracture rate over 5 yr in this age group is high irrespective of the population that has been studied. Secondly, bone density testing has been shown to detect individuals at high risk of fracture in this age group (10, 11). Finally, there is evidence from a large trial that targeting treatment at individuals with osteoporosis (T score –2.5) but not osteopenia (T score –1.6) reduces fracture rates at many sites with acceptable safety (12). Another method of selecting women for treatment involves the use of historical risk factors such as low body weight, previous fractures, and corticosteroid use with or without bone densitometery. This approach is often supported by third part payers by allowing bone densitometery rebates in subjects with the risk factors. For example, there is good evidence that previous vertebral and appendicular fracture predisposes to future vertebral fracture (13,14). The relative advantages of selective bone density testing using risk factors such as previous fracture compared to nonselective bone density testing in detecting high-risk subjects suggests an advantage from the combined approach. Furthermore, there are treatments of proven efficacy in reducing fractures in patients selected using a bone density and prevalent fracture strategy (15).
Volume 2, 1999
Osteoporosis Detection and Treatment Finally, a whole population intervention strategy could be undertaken without trying to detect highrisk individuals. In view of the very high rates of fracture in elderly subjects irrespective of the precise population or classification of fracture used, it would seem reasonable to target this group for a public health strategy. In view of good randomized controlled trial evidence of efficacy for calcium and vitamin D treatment in appendicular fracture prevention in countries in northern latitudes, these interventions should be seriously considered for a whole population intervention (16,17). However, long-term compliance with calcium supplementation is poor (18). Thus, careful consideration of methods of introducing these treatments should be undertaken, for example, by a food fortification approach. It is clear that achieving effective fracture prevention will require a variety of interventions targeted to particular age and risk groups. The availability of technology for early detection of fracture propensity coupled with effective treatments suggests that we should, in the near future, be able to significantly reduce age-specific fracture rates.
107
6.
7.
8.
9.
10. 11.
12.
13.
References 1. Jones G, Scott FS. 1999. Low bone mass in premenopausal parous women: identification and the effect of an information and bone density feedback program. J Clin Densitometry 2:109–115. 2. Donaldson LJ, Cook A, Thomson RG. 1990. Incidence of fractures in a geographically defined population. J Epidemiol Community Health 44:241–245. 3. Honkanen R, Tuppurainen M, Kroger H, Alhava E, Saarikoski S. 1998. Relationships between risk factors and fractures differ by type of fracture: a population based study of 12192 perimenopausal women. Osteoporosis Int 8:25–31. 4. Adinoff AD, Hollister JR. 1983. Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med 309:265–308. 5. Sanders KM, Pasco JA, Ugoni AM, Nicholson GC, Seeman E, Martin TJ, et al. 1998. The exclusion of high trauma fractures may underestimate the prevalence of bone fragility
Journal of Clinical Densitometry
14.
15.
16.
17.
18.
fractures in the community: the Geelong Osteoporosis Study. J Bone Miner Res 13:1337–1342. Seeley DG, Browner WS, Nevitt MC, Genant HK, Scott JC, Cummings SR. 1991. Which fractures are associated with low appendicular bone mass in elderly women? Ann. Intern Med 115:837–842. Eddy DM, Johnston CC, Cummings SR, Dawson-Hughes B, Lindsay R, Melton LJIII, et al. 1998. Osteoporosis: review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Osteoporosis Int 8:S7–S80. Knowelden J, Buhr AJ, Dunbar O. 1964. Incidence of fractures in persons over 35 years of age. Br J Prev Soc Med 18:130–141. Jones G, Nguyen T, Sambrook PN, Kelly PJ, Gilbert C, Eisman JA. 1994. Symptomatic fracture incidence in elderly men and women: the Dubbo osteoporosis epidemiology study (DOES). Osteoporosis Int 4:277–282. Johnston CC, Slemenda CW, Melton LJ, 1991. Clinical use of bone densitometry. N Engl J Med 324:1105–1109. Nevitt MC, Johnell O, Black DM, Ensrud K, Genant HK, Cummings SR. 1994. Bone mineral density predicts nonspine fractures in very elderly women. Osteoporosis Int 4:325–331. Cummings SR. 1998. Effect of alendronateon risk of fracture in women with low bone density but without vertebral fracture: Results from the Fracture Intervention Trial. JAMA 280:2077–2082. Wasnich RD, Davis JW, Ross PD. 1994. Spine fracture risk is predicted by non-spine fractures. Osteoporosis Int 4:1–5. Ross PD, Davis JW, Epstein RS, Wasnich RD. 1991. Preexisting fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med 114:919–923. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. 1996. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541. Dawson-Hughes B, Harris SS, Khall EA, Dallal GE. 1997. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 337:670–676. Chapuy MC, Arlot MF, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. 1992. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 327:1637–1642. Devine A, Prince RL, Bell R. 1996. Nutritional effect of calcium supplementation by skim milk powder or calcium tablets on total nutrient intake in postmenopausal women. Am J Clin Nutr 64:731–737.
Volume 2, 1999