Comment
weighed against potential risks posed by the patient’s comorbid disorders. We recommend the use of lifestyle modification to treat individuals with sustained obesity, but it should be only one component of a multimodal treatment strategy. It is also important for clinicians to note that weight losses of only 5–10% of initial bodyweight are sufficient for clinically meaningful reductions in weight-related biomarkers, despite the fact that this level of weight loss might be disappointing to some patients with more aesthetically-driven goals. Finally, we encourage clinicians to monitor patients’ weight-loss progress and adapt treatment strategies over time. Specific plans to maintain lost weight should be developed. For example, an individual might be initially successful in losing weight with lifestyle modification but need pharmacotherapy to sustain clinically meaningful weight loss. See panel for a summary of recommendations for the prevention and treatment of obesity, and the recently published NIH working group report14 for recommendations for weight loss maintenance. We urge individuals in the medical and scientific community to seek a better understanding of the biological factors that maintain obesity and to approach it as a disease that cannot be reliably prevented or cured with current frontline methods.
Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (RFK); Center for Lifestyle Medicine, Northwestern Medical Faculty Foundation, Chicago, IL, USA (RFK); and Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA (TAW) [email protected] CNO reports grants from Accera, and non-financial support from ProBar. AGT reports non-financial support from Nutrisystem. RFK reports personal fees from Vivus, Takeda, and Novo Nordisk and grants from Weight Watchers. TAW reports personal fees from Nutrisystem, Orexigen Pharmaceutical, Novo Nordisk, Boehringer Ingelheim, Guilford Press, and Shire Pharmaceutical and grants from Novo Nordisk, Weight Watchers, and NutriSystem. 1 2 3
4 5 6 7
8
9
10
*Christopher N Ochner, Adam G Tsai, Robert F Kushner, Thomas A Wadden Mount Sinai Adolescent Health Center, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10128, USA (CNO); New York Obesity Nutrition Research Center, Columbia University Medical Center, New York, NY, USA (CNO); Kaiser Permanente of Colorado, Departments of Internal Medicine and Metabolic-Surgical Weight Management, Denver, CO, USA (AGT); University of Colorado School of Medicine, Division of General Internal Medicine, Aurora, CO, USA (AGT); Department of
11
12
13 14
Colbert JA, Sushrut J. Training clinicians to manage obesity—back to the drawing board. N Engl J Med 2013; 369: 1389–91. Puhl RM, Heuer CA. Obesity stigma: important considerations for public health. Am J Public Health 2010; 100: 1019–28. Ochner CN, Barrios DM, Lee CD, Pi-Sunyer FX. Biological mechanisms that promote weight regain following weight loss in obese humans. Physiol Behav 2013; 120: 106–13. Kenny PJ. Reward mechanisms in obesity: new insights and future directions. Neuron 2011; 69: 664–79. Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes 2010; 34 (suppl 1): S47–55. Rosenbaum M, Leibel RL. 20 years of leptin: role of leptin in energy homeostasis in humans. J Endocrinol 2014; 223: T83–96. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363: 245-256. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377: 1341–52. Wadden TA, Berkowitz RI, Womble LG, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005; 353: 2111–20. Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med 2013; 273: 219–34. le Roux CW, Welbourn R, Werling M, et al. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg 2007; 246: 780–85. Ochner CN, Kwok Y, Conceicao E, et al. Selective reduction in neural responses to high calorie foods following gastric bypass surgery. Ann Surg 2011; 253: 502–07. Jensen MD, Ryan DH, Donato KA, et al. Guidelines (2013) for managing overweight and obesity in adults. Obesity 2014; 22: S1–410. MacLean PS, Wing RR, Davidson T, et al. NIH working group report: innovative research to improve maintenance of weight loss. Obesity 2015; 23: 7–15.
Diagnostic criteria for osteoporosis should be expanded See Online for interviews with Alexandra Papaioannou and John Schousboe
234
As a relatively newly classified chronic disease, scientific enquiry about pathophysiology, diagnosis, and treatment for osteoporosis has rapidly increased in the past three decades. Under the direction of the National Bone Health Alliance, a working group has proposed expansion of the diagnostic criteria for osteoporosis in men and postmenopausal women aged 50 years and older to include individuals with any of the following:
a hip fracture (with or without bone mineral density [BMD] testing); low bone mass as determined by BMD and a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture; or raised fracture risk based on the WHO fracture risk algorithm, FRAX. We propose that this is a prudent approach and that it reflects the present understanding of bone fragility and fracture-risk prediction. www.thelancet.com/diabetes-endocrinology Vol 3 April 2015
Comment
www.thelancet.com/diabetes-endocrinology Vol 3 April 2015
markers are used in addition to low BMD.7 In the FIT trial, bisphosphonates decreased vertebral fracture risk in patients with low bone mass.8 Clinical predictors of fracture have powerful casefinding potential, particularly when used in older individuals. The FRAX tool, in addition to using clinical risk factors, recommends input of BMD to establish the 10 year probability of a major fracture. However, FRAX alone has comparable predictive ability as FRAX with BMD and identifies patients at risk who are responsive to pharmaceutical intervention.9 A model involving FRAX scores without BMD input has not been validated in residents in nursing homes. Thus, in contexts in which obtaining of a BMD measurement is not possible for fracture risk assessment, clinical risk factors might be sufficient, especially in frail elderly people. With a rapidly ageing society, it is crucial to consider the effect of management of osteoporosis and ultimately prevention of fractures in a group that is already at higher risk due to age-related bone loss. For a resident of a nursing home or a housebound elderly person, obtaining a BMD result is often impractical or unattainable. Thus, history taking and physical examination to identify previous fractures is of even more importance in this population.10 The Ontario Osteoporosis Strategy for long-term care has recently completed guidelines specific for frail elderly residents These guidelines specify that residents identified as being at high risk for fractures and receiving osteoporosis treatments before admission into longterm care should continue to have this classification applied at admission.
For the Ontario Osteoporosis Strategy see http://www. osteoporosislongtermcare.ca
Dan Aucante/Science Photo Library
With the emergence of bone densitometry as a reliable measure, in 1994 WHO proposed the first operational definition of osteoporosis based on BMD T-scores.1 These criteria were established based on dual-energy X-ray absorptiometry (DXA) as the technique to quantify bone mass.2 Given that the diagnostic cut-point for osteoporosis (more than 2·5 standard deviations below the young average value) is based on a statistical distribution, the absolute BMD values for osteoporosis diagnosed in this way differ according to the site measured, technique, equipment, and reference population. In the past decade, there have been at least two paradigm shifts in the diagnosis and management of osteoporosis. The first major shift was the incorporation of clinical risk factors into fracture risk prediction. The FRAX tool developed by WHO, which can be used to predict fracture risk with or without BMD values, has been validated worldwide. Since 2010, Canadian osteoporosis guidelines have incorporated clinical risk factors for diagnosis of osteoporosis in addition to BMD,3 similar to other countries.4 Individuals at high risk of fractures are those with previous fracture of the hip or spine, more than one previous non-vertebral fracture (excluding hands, feet, and ankles), or those who have recently used glucocorticoids and have had one previous fracture. Numbers needed to treat to prevent further fractures are low and intervention is cost-effective in these high-risk individuals.3 The second shift has been recognition of the importance of bone quality, in addition to density, as a key component of bone strength. Bone quality can be thought of as a complex set of interdependent factors that affect bone strength, including structural (eg, geometry and microarchitecture) and material (eg, mineral crystal size, quality of collagen, and microdamage or microfracture) properties of bone.5 Although the use of bone quality measures in clinical diagnosis of osteoporosis is still being investigated, several techniques can be used to estimate bone quality. These shifts are based on the concept that BMD alone does not adequately predict fracture risk. Relatively small increases in BMD with treatment can substantially reduce fracture risk. More than half of fractures occur in the non-osteoporotic range, indicating relatively poor sensitivity of BMD.6,7 Fracture prediction in women with low bone mass (T-score between –2·5 and –2·0) is improved when previous fracture and bone turnover
235
Comment
The absolute risk reduction of an intervention is greatest for patients with more severe underlying disease (ie, at high risk of the adverse event).11 Previous fracture is a powerful predictor of a future fracture;12 however, a substantial care gap has been created in treatment of individuals with fracture in part due to an overemphasis on BMD values. Previous fracture, particularly hip or vertebral fracture, should undoubtedly be sufficient criteria for the diagnosis of osteoporosis in the absence of BMD, particularly in frail elderly individuals. *Alexandra Papaioannou, Courtney Kennedy Division of Geriatric Medicine, McMaster University, St Peter’s Hospital, GERAS Centre, Hamilton, ON L8M 1W9, Canada (AP, CK) [email protected]
4
5
6
7
8
9 10
11
AP reports grants and personal fees from Amgen, grants and personal fees from Eli Lilly, grants from Merck Canada, and grants from Werner Chilcott, outside the submitted work. CK declares no competing interests. 1
2 3
Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994; 4: 368–81. Kanis JA. An update on the diagnosis of osteoporosis. Curr Rheumatol Rep 2000; 2: 62–66. Papaioannou A, Morin S, Cheung AM, et al, for the Scientific Advisory Council of Osteoporosis Canada. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 2010; 182: 1864–73.
12
National Institute for Health and Care Excellence. Osteoporosis: assessing the risk of fragility fracture 2012. NICE guidelines CG146. http://www.nice. org.uk/guidance/cg146. (accessed Jan 20, 2015). Felsenberg D, Boonen S. The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 2005; 27: 1–11. Schuit S, Van der Klift M, Weel A, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 2004; 34: 195–202. Sornay-Rendu E, Munoz F, Duboeuf F, Delmas PD. Rate of forearm bone loss is associated with an increased risk of fracture independently of bone mass in postmenopausal women: the OFELY study. J Bone Miner Res 2005; 20: 1929–35. Quandt SA, Thompson DE, Schneider DL, Nevitt MC, Black DM, for the Fracture Intervention Trial Research Group. Effect of alendronate on vertebral fracture risk in women with bone mineral density T scores of-1.6 to -2.5 at the femoral neck: the Fracture Intervention Trial. Mayo Clin Proc 2005; 80: 343–49. Kanis JA, McCloskey E, Johansson H, Oden A, Leslie WD. FRAX(®) with and without bone mineral density. Calcif Tissue Int 2012; 90: 1–13. Greenspan SL, Perera S, Nace D, et al. FRAX or fiction: determining optimal screening strategies for treatment of osteoporosis in residents in long-term care facilities. J Am Geriatr Soc 2012; 60: 684–90. Barratt A, Wyer PC, Hatala R, et al, for the Evidence-Based Medicine Teaching Tips Working Group. Tips for learners of evidence-based medicine: 1. Relative risk reduction, absolute risk reduction and number needed to treat. CMAJ 2004; 171: 353–58. Gehlbach S1, Saag KG, Adachi JD, et al. Previous fractures at multiple sites increase the risk for subsequent fractures: the Global Longitudinal Study of Osteoporosis in Women. J Bone Miner Res 2012; 27: 645–53.
DNA Illustrations/Science Photo Library
Diagnostic criteria for osteoporosis should not be expanded
See Online for interviews with Alexandra Papaioannou and John Schousboe
236
In 1994, WHO1 defined osteoporosis as a disorder of skeletal fragility with the hallmark of low bone mass (defined as femoral neck bone mineral density [BMD] 2·5 or more standard deviations less than the average of healthy 30-year-old women [T-score –2·5 or less]), or a prevalent radiographic vertebral fracture (indicative of bone structural weakness and fragility). This definition is also the clinical criteria for the diagnosis of osteoporosis in most countries, although clinicians in the USA often use a T-score of –2·5 or less at the lumbar spine, total hip, or femoral neck.2 However, most individuals who have low-trauma age-related fractures do not have osteoporosis by BMD criteria,3 prompting efforts to use fracture risk algorithms to identify, as candidates for drug therapy, people who are at higher absolute risk of fracture. Several US organisations have recommended 10 year fracture risk (by the FRAX algorithm) intervention thresholds of 3% for hip fracture and 20% for major osteoporotic fracture (clinical vertebral,
forearm, hip, or proximal humerus fracture) as cutpoints for starting drug treatment in adults aged 50 years and older. A recent position statement from the National Bone Health Alliance Working Group4 (a consortium of musculoskeletal societies and industry partners) proposed expansion of the definition of osteoporosis to include adults aged 50 years and older with BMD T-score of –2·5 or less at spine or hip, recent hip or clinical vertebral fracture, or FRAX 10 year fracture probability higher than either of the intervention thresholds defined above. Because of its inclusion of FRAX intervention thresholds, this expanded definition would greatly increase the proportion of US adults aged 65 years and older who are labelled as having a diagnosis of osteoporosis from an estimated 40% to 72% of women5 and from 7% to 34% of men.6 Broadening of the definition of a disease can have adverse consequences, including labelling a substantial www.thelancet.com/diabetes-endocrinology Vol 3 April 2015
weighed against potential risks posed by the patient’s comorbid disorders. We recommend the use of lifestyle modification to treat individuals with sustained obesity, but it should be only one component of a multimodal treatment strategy. It is also important for clinicians to note that weight losses of only 5–10% of initial bodyweight are sufficient for clinically meaningful reductions in weight-related biomarkers, despite the fact that this level of weight loss might be disappointing to some patients with more aesthetically-driven goals. Finally, we encourage clinicians to monitor patients’ weight-loss progress and adapt treatment strategies over time. Specific plans to maintain lost weight should be developed. For example, an individual might be initially successful in losing weight with lifestyle modification but need pharmacotherapy to sustain clinically meaningful weight loss. See panel for a summary of recommendations for the prevention and treatment of obesity, and the recently published NIH working group report14 for recommendations for weight loss maintenance. We urge individuals in the medical and scientific community to seek a better understanding of the biological factors that maintain obesity and to approach it as a disease that cannot be reliably prevented or cured with current frontline methods.
Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA (RFK); Center for Lifestyle Medicine, Northwestern Medical Faculty Foundation, Chicago, IL, USA (RFK); and Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA (TAW) [email protected] CNO reports grants from Accera, and non-financial support from ProBar. AGT reports non-financial support from Nutrisystem. RFK reports personal fees from Vivus, Takeda, and Novo Nordisk and grants from Weight Watchers. TAW reports personal fees from Nutrisystem, Orexigen Pharmaceutical, Novo Nordisk, Boehringer Ingelheim, Guilford Press, and Shire Pharmaceutical and grants from Novo Nordisk, Weight Watchers, and NutriSystem. 1 2 3
4 5 6 7
8
9
10
*Christopher N Ochner, Adam G Tsai, Robert F Kushner, Thomas A Wadden Mount Sinai Adolescent Health Center, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10128, USA (CNO); New York Obesity Nutrition Research Center, Columbia University Medical Center, New York, NY, USA (CNO); Kaiser Permanente of Colorado, Departments of Internal Medicine and Metabolic-Surgical Weight Management, Denver, CO, USA (AGT); University of Colorado School of Medicine, Division of General Internal Medicine, Aurora, CO, USA (AGT); Department of
11
12
13 14
Colbert JA, Sushrut J. Training clinicians to manage obesity—back to the drawing board. N Engl J Med 2013; 369: 1389–91. Puhl RM, Heuer CA. Obesity stigma: important considerations for public health. Am J Public Health 2010; 100: 1019–28. Ochner CN, Barrios DM, Lee CD, Pi-Sunyer FX. Biological mechanisms that promote weight regain following weight loss in obese humans. Physiol Behav 2013; 120: 106–13. Kenny PJ. Reward mechanisms in obesity: new insights and future directions. Neuron 2011; 69: 664–79. Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes 2010; 34 (suppl 1): S47–55. Rosenbaum M, Leibel RL. 20 years of leptin: role of leptin in energy homeostasis in humans. J Endocrinol 2014; 223: T83–96. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363: 245-256. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377: 1341–52. Wadden TA, Berkowitz RI, Womble LG, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005; 353: 2111–20. Sjöström L. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med 2013; 273: 219–34. le Roux CW, Welbourn R, Werling M, et al. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg 2007; 246: 780–85. Ochner CN, Kwok Y, Conceicao E, et al. Selective reduction in neural responses to high calorie foods following gastric bypass surgery. Ann Surg 2011; 253: 502–07. Jensen MD, Ryan DH, Donato KA, et al. Guidelines (2013) for managing overweight and obesity in adults. Obesity 2014; 22: S1–410. MacLean PS, Wing RR, Davidson T, et al. NIH working group report: innovative research to improve maintenance of weight loss. Obesity 2015; 23: 7–15.
Diagnostic criteria for osteoporosis should be expanded See Online for interviews with Alexandra Papaioannou and John Schousboe
234
As a relatively newly classified chronic disease, scientific enquiry about pathophysiology, diagnosis, and treatment for osteoporosis has rapidly increased in the past three decades. Under the direction of the National Bone Health Alliance, a working group has proposed expansion of the diagnostic criteria for osteoporosis in men and postmenopausal women aged 50 years and older to include individuals with any of the following:
a hip fracture (with or without bone mineral density [BMD] testing); low bone mass as determined by BMD and a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture; or raised fracture risk based on the WHO fracture risk algorithm, FRAX. We propose that this is a prudent approach and that it reflects the present understanding of bone fragility and fracture-risk prediction. www.thelancet.com/diabetes-endocrinology Vol 3 April 2015
Comment
www.thelancet.com/diabetes-endocrinology Vol 3 April 2015
markers are used in addition to low BMD.7 In the FIT trial, bisphosphonates decreased vertebral fracture risk in patients with low bone mass.8 Clinical predictors of fracture have powerful casefinding potential, particularly when used in older individuals. The FRAX tool, in addition to using clinical risk factors, recommends input of BMD to establish the 10 year probability of a major fracture. However, FRAX alone has comparable predictive ability as FRAX with BMD and identifies patients at risk who are responsive to pharmaceutical intervention.9 A model involving FRAX scores without BMD input has not been validated in residents in nursing homes. Thus, in contexts in which obtaining of a BMD measurement is not possible for fracture risk assessment, clinical risk factors might be sufficient, especially in frail elderly people. With a rapidly ageing society, it is crucial to consider the effect of management of osteoporosis and ultimately prevention of fractures in a group that is already at higher risk due to age-related bone loss. For a resident of a nursing home or a housebound elderly person, obtaining a BMD result is often impractical or unattainable. Thus, history taking and physical examination to identify previous fractures is of even more importance in this population.10 The Ontario Osteoporosis Strategy for long-term care has recently completed guidelines specific for frail elderly residents These guidelines specify that residents identified as being at high risk for fractures and receiving osteoporosis treatments before admission into longterm care should continue to have this classification applied at admission.
For the Ontario Osteoporosis Strategy see http://www. osteoporosislongtermcare.ca
Dan Aucante/Science Photo Library
With the emergence of bone densitometry as a reliable measure, in 1994 WHO proposed the first operational definition of osteoporosis based on BMD T-scores.1 These criteria were established based on dual-energy X-ray absorptiometry (DXA) as the technique to quantify bone mass.2 Given that the diagnostic cut-point for osteoporosis (more than 2·5 standard deviations below the young average value) is based on a statistical distribution, the absolute BMD values for osteoporosis diagnosed in this way differ according to the site measured, technique, equipment, and reference population. In the past decade, there have been at least two paradigm shifts in the diagnosis and management of osteoporosis. The first major shift was the incorporation of clinical risk factors into fracture risk prediction. The FRAX tool developed by WHO, which can be used to predict fracture risk with or without BMD values, has been validated worldwide. Since 2010, Canadian osteoporosis guidelines have incorporated clinical risk factors for diagnosis of osteoporosis in addition to BMD,3 similar to other countries.4 Individuals at high risk of fractures are those with previous fracture of the hip or spine, more than one previous non-vertebral fracture (excluding hands, feet, and ankles), or those who have recently used glucocorticoids and have had one previous fracture. Numbers needed to treat to prevent further fractures are low and intervention is cost-effective in these high-risk individuals.3 The second shift has been recognition of the importance of bone quality, in addition to density, as a key component of bone strength. Bone quality can be thought of as a complex set of interdependent factors that affect bone strength, including structural (eg, geometry and microarchitecture) and material (eg, mineral crystal size, quality of collagen, and microdamage or microfracture) properties of bone.5 Although the use of bone quality measures in clinical diagnosis of osteoporosis is still being investigated, several techniques can be used to estimate bone quality. These shifts are based on the concept that BMD alone does not adequately predict fracture risk. Relatively small increases in BMD with treatment can substantially reduce fracture risk. More than half of fractures occur in the non-osteoporotic range, indicating relatively poor sensitivity of BMD.6,7 Fracture prediction in women with low bone mass (T-score between –2·5 and –2·0) is improved when previous fracture and bone turnover
235
Comment
The absolute risk reduction of an intervention is greatest for patients with more severe underlying disease (ie, at high risk of the adverse event).11 Previous fracture is a powerful predictor of a future fracture;12 however, a substantial care gap has been created in treatment of individuals with fracture in part due to an overemphasis on BMD values. Previous fracture, particularly hip or vertebral fracture, should undoubtedly be sufficient criteria for the diagnosis of osteoporosis in the absence of BMD, particularly in frail elderly individuals. *Alexandra Papaioannou, Courtney Kennedy Division of Geriatric Medicine, McMaster University, St Peter’s Hospital, GERAS Centre, Hamilton, ON L8M 1W9, Canada (AP, CK) [email protected]
4
5
6
7
8
9 10
11
AP reports grants and personal fees from Amgen, grants and personal fees from Eli Lilly, grants from Merck Canada, and grants from Werner Chilcott, outside the submitted work. CK declares no competing interests. 1
2 3
Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994; 4: 368–81. Kanis JA. An update on the diagnosis of osteoporosis. Curr Rheumatol Rep 2000; 2: 62–66. Papaioannou A, Morin S, Cheung AM, et al, for the Scientific Advisory Council of Osteoporosis Canada. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 2010; 182: 1864–73.
12
National Institute for Health and Care Excellence. Osteoporosis: assessing the risk of fragility fracture 2012. NICE guidelines CG146. http://www.nice. org.uk/guidance/cg146. (accessed Jan 20, 2015). Felsenberg D, Boonen S. The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 2005; 27: 1–11. Schuit S, Van der Klift M, Weel A, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 2004; 34: 195–202. Sornay-Rendu E, Munoz F, Duboeuf F, Delmas PD. Rate of forearm bone loss is associated with an increased risk of fracture independently of bone mass in postmenopausal women: the OFELY study. J Bone Miner Res 2005; 20: 1929–35. Quandt SA, Thompson DE, Schneider DL, Nevitt MC, Black DM, for the Fracture Intervention Trial Research Group. Effect of alendronate on vertebral fracture risk in women with bone mineral density T scores of-1.6 to -2.5 at the femoral neck: the Fracture Intervention Trial. Mayo Clin Proc 2005; 80: 343–49. Kanis JA, McCloskey E, Johansson H, Oden A, Leslie WD. FRAX(®) with and without bone mineral density. Calcif Tissue Int 2012; 90: 1–13. Greenspan SL, Perera S, Nace D, et al. FRAX or fiction: determining optimal screening strategies for treatment of osteoporosis in residents in long-term care facilities. J Am Geriatr Soc 2012; 60: 684–90. Barratt A, Wyer PC, Hatala R, et al, for the Evidence-Based Medicine Teaching Tips Working Group. Tips for learners of evidence-based medicine: 1. Relative risk reduction, absolute risk reduction and number needed to treat. CMAJ 2004; 171: 353–58. Gehlbach S1, Saag KG, Adachi JD, et al. Previous fractures at multiple sites increase the risk for subsequent fractures: the Global Longitudinal Study of Osteoporosis in Women. J Bone Miner Res 2012; 27: 645–53.
DNA Illustrations/Science Photo Library
Diagnostic criteria for osteoporosis should not be expanded
See Online for interviews with Alexandra Papaioannou and John Schousboe
236
In 1994, WHO1 defined osteoporosis as a disorder of skeletal fragility with the hallmark of low bone mass (defined as femoral neck bone mineral density [BMD] 2·5 or more standard deviations less than the average of healthy 30-year-old women [T-score –2·5 or less]), or a prevalent radiographic vertebral fracture (indicative of bone structural weakness and fragility). This definition is also the clinical criteria for the diagnosis of osteoporosis in most countries, although clinicians in the USA often use a T-score of –2·5 or less at the lumbar spine, total hip, or femoral neck.2 However, most individuals who have low-trauma age-related fractures do not have osteoporosis by BMD criteria,3 prompting efforts to use fracture risk algorithms to identify, as candidates for drug therapy, people who are at higher absolute risk of fracture. Several US organisations have recommended 10 year fracture risk (by the FRAX algorithm) intervention thresholds of 3% for hip fracture and 20% for major osteoporotic fracture (clinical vertebral,
forearm, hip, or proximal humerus fracture) as cutpoints for starting drug treatment in adults aged 50 years and older. A recent position statement from the National Bone Health Alliance Working Group4 (a consortium of musculoskeletal societies and industry partners) proposed expansion of the definition of osteoporosis to include adults aged 50 years and older with BMD T-score of –2·5 or less at spine or hip, recent hip or clinical vertebral fracture, or FRAX 10 year fracture probability higher than either of the intervention thresholds defined above. Because of its inclusion of FRAX intervention thresholds, this expanded definition would greatly increase the proportion of US adults aged 65 years and older who are labelled as having a diagnosis of osteoporosis from an estimated 40% to 72% of women5 and from 7% to 34% of men.6 Broadening of the definition of a disease can have adverse consequences, including labelling a substantial www.thelancet.com/diabetes-endocrinology Vol 3 April 2015
