William D. Leslie

2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary

See related commentary by Kanis, page [1829][1] Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

The Incidence of Fracture among Patients with Inflammatory Bowel Disease: A Population-Based Cohort Study

The prevalence of osteopenia among patients with inflammatory bowel disease ranges from 40% to 50%, and frank osteoporosis is seen in 2% to 30% of patients (1-5). These estimates are based on measurement of bone mineral density, in which osteoporosis is defined as a bone mass T-score less than 2.5 (6). Much has been written about the prevalence and causes of osteopenia, and a few reports have been published on the treatment of osteopenia in inflammatory bowel disease (7-9). However, the clinical importance of osteopenia among persons with inflammatory bowel disease is unclear because no data have been published on the actual risk for fracture in persons with inflammatory bowel disease. The most common fractures associated with osteoporosis are those of the hip, spine, and distal radius (10). Rib fractures are also of interest since they are common among persons with low bone mass (11). We sought to determine whether persons with inflammatory bowel disease had an increased risk for these fractures compared with persons without inflammatory bowel disease. Methods The incidence of fracture in a cohort of persons with inflammatory bowel disease was compared with that in a cohort of persons without inflammatory bowel disease, matched 1 to 10 to the inflammatory bowel disease cohort by age, sex, and geographic location of residence. The inflammatory bowel disease cohort (n =6027) consisted of persons in the population-based University of Manitoba IBD Database, which has been described elsewhere (12). In brief, the database was developed by using Manitoba Health administrative databases. Manitoba Health (Government of Manitoba) provides comprehensive health care coverage for residents of Manitoba, Canada (population, 1.14 million). Since Manitoba residents are not obliged to pay premiums for health care coverage, nonparticipation in the plan is rare. Manitoba Health maintains computerized databases of physician services and hospitalizations for all persons registered with the system. Each physician service record includes information on the identity of the patient, the date of service, services provided, and diagnosis, which is subsequently coded as a three-digit International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) code. After each hospitalization, a detailed abstract is created that includes up to 16 diagnoses coded as five-digit ICD-9-CM codes. By extracting physician service records and hospitalizations for all Manitoba residents from 1984 to 1997, we created a population-based database of all persons who had received a diagnosis of Crohn disease (ICD-9-CM code 555.xx) or ulcerative colitis (ulcerative colitis) (ICD-9-CM code 556.xx). The cohort of persons without inflammatory bowel disease was created by randomly selecting 10 persons without inflammatory bowel disease from the Manitoba Health population registry. These 60 270 controls were matched to persons with inflammatory bowel disease by year of birth, sex, and postal area of residence at the date of diagnosis of the index case of inflammatory bowel disease. The incidence of hospitalization for hip fracture was calculated by using the Manitoba Health administrative database for hospital discharge abstracts (using ICD-9-CM code 820.xx). Outpatient health system contacts and hospitalization contacts for spine fractures (ICD-9-CM code 806.xx), rib fractures (ICD-9-CM 807.0x to 807.1x) and wrist/forearm fractures (ICD-9-CM 813.xx) were analyzed in a similar fashion. Incidence rates were calculated on the basis of person-years of follow-up for 1984 to 1997. Incidence rate ratios (IRRs) and 95% CIs were calculated by comparing the incidence of fracture in persons with inflammatory bowel disease with that in controls, using Poisson regression. To determine whether enhanced physician contact and an increased frequency of radiography in persons with inflammatory bowel disease influenced the estimated incidence of rib, forearm, and spine fractures, we performed supplementary analyses in which we excluded all persons who had undergone radiography of the chest, ribs, abdomen, or spine in the 2 years before the date of fracture. The construction of the University of Manitoba IBD Database and its use in clinical studies were approved by the University of Manitoba Research Ethics Board and by the Access and Confidentiality Committee of Manitoba Health and was funded by the National Health and Research Development Program of Canada. Comparison of persons with inflammatory bowel disease with matched controls was performed without external funding. Results Person-years of follow-up were 21 340 for Crohn disease and 19 665 for ulcerative colitis. The mean age at the start of follow-up was 36.3 16.7 years for persons with Crohn disease and 42.0 18.0 years for persons with ulcerative colitis. Forty-one percent of persons with Crohn disease and 50% of those with ulcerative colitis were male. Overall, 405 incident fractures occurred among persons with inflammatory bowel disease, for an incidence of 98.8 per 10 000 persons (Table 1). The incidence of fractures among persons with inflammatory bowel disease increased with advancing age for all fracture sites (Table 1). This was particularly true for hip fractures, which occurred mostly among persons older than 60 years of age and were rare among persons younger than 40 years of age. The overall crude incidence rate of fractures was higher in persons with ulcerative colitis than those with Crohn disease. This finding reflects the older age distribution of persons with ulcerative colitis, since fracture rates were similar in each age stratum (Table 1). Table 1. Crude Incidence of Fracture among Persons with Inflammatory Bowel Disease in Manitoba, Canada, 19841997 Compared with controls, persons with inflammatory bowel disease had a significantly elevated incidence of fracture at the hip (IRR, 1.59 [95% CI, 1.27 to 2.00]; P<0.001), spine (IRR, 1.74 [CI, 1.34 to 2.24]; P<0.001), wrist/forearm (IRR, 1.33 [CI, 1.11 to 1.58]; P=0.001), and rib (IRR, 1.25 [CI, 1.02 to 1.52]; P=0.03) (Table 2). For these fractures combined, persons with inflammatory bowel disease had an increased incidence of approximately 40% (IRR, 1.41 [CI, 1.27 to 1.56]; P<0.001). The patterns of increased fracture incidence were similar in persons with Crohn disease and those with ulcerative colitis (Table 2) and in men and women with inflammatory bowel disease (data not shown). When fractures in persons who had had radiography in the previous 2 years were excluded from analysis, the results changed little for fractures of the spine (IRR, 1.81 [CI, 1.39 to 2.37]), forearm (IRR, 1.37 [CI, 1.16 to 1.63]), and rib (IRR, 1.27 [CI, 1.03 to 1.56]). Table 2. Age-Specific Incidence Rate Ratios for Fracture in Persons with Inflammatory Bowel Disease, Manitoba, Canada, 19841997 Discussion We found significantly increased rates of hip, spine, and forearm fractures among persons with inflammatory bowel disease compared with persons without this disease in the general population. Because our rates of fracture were calculated from administrative health data, it is important to discuss the accuracy of this data source. Inaccuracies in hospital discharge coding have been reported (13, 14). The accuracy of hospital discharge coding was recently reported for hip fracture admissions in Baltimore, Maryland, in which variations in comorbid diagnoses or complications on hospital face sheets ranged from 12% to 17% (15). However, the rate of miscoding hip fracture in the Baltimore hospitals studied is rare (Hawkes WG. Personal communication) and was found to be rare in studies using hospital discharge abstracts data in Pittsburgh, Pennsylvania; Portland, Oregon; and Minneapolis, Minnesota (Fox KM. Personal communication). Data from Manitoba have shown excellent correlation (>95%) for hip fracture on linkage between hospital separation diagnosis and physician billing data (16). Since fractures at the spine, rib, and forearm may not necessitate hospitalization and the accuracy of physician outpatient billing records is less certain, we are less confident in our estimates of the actual incidence of these fractures. Furthermore, spine or rib fracture may sometimes go undetected. This may introduce a detection bias, since patients with inflammatory bowel disease may have more frequent physician visits and radiography for other indications and therefore may be more likely to have these fractures diagnosed. To determine whether such bias accounted for increased rates of rib, spine, and forearm fracture, we conducted supplementary analyses excluding persons who had had radiography of the chest, ribs, spine, or abdomen in the 2 years before the fracture date. Results of this analysis did not change the overall results appreciably, suggesting that enhanced radiologic screening does not fully explain the higher rates of these fractures among persons with inflammatory bowel disease. Our finding of increased rates of fracture in persons with inflammatory bowel disease indicates that lower bone mineral density in this population is clinically relevant. It will now be important to delineate risk factors for low bone density and fracture in inflammatory bowel disease. Although use of corticosteroids in inflammatory bowel disease may be a factor (17), diminished bone mass in inflammatory bowel disease in the absence of corticosteroid use has been reported (18). Since treatment with bisphosphonates has been shown to ameliorate corticosteroid-induced osteoporosis (19), it will be particularly important to clarify the relative contribution of corticosteroid use to development of osteoporosis in inflammatory bowel disease. Other factors may also play a role. Studies have shown that patients with Crohn disease are more likely to smoke and patients with inflammatory bowel disease may have lower levels of sex hormones and ingest less than the recommended daily amount of calcium and

Use of proton pump inhibitors and risk of osteoporosis-related fractures.

Background: The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures. Methods: We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years. Results: We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16–3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02–2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68–12.29, p = 0.002). Interpretation: Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.

Trends in Hip Fracture Rates in Canada

CONTEXT Hip fractures are a public health concern because they are associated with significant morbidity, excess mortality, and the majority of the costs directly attributable to osteoporosis. OBJECTIVE To examine trends in hip fracture rates in Canada. DESIGN, SETTING, AND PATIENTS Ecologic trend study using nationwide hospitalization data for 1985 to 2005 from a database at the Canadian Institute for Health Information. Data for all patients with a hospitalization for which the primary reason was a hip fracture (570,872 hospitalizations) were analyzed. MAIN OUTCOME MEASURES Age-specific and age-standardized hip fracture rates. RESULTS There was a decrease in age-specific hip fracture rates (all P for trend <.001). Over the 21-year period of the study, age-adjusted hip fracture rates decreased by 31.8% in females (from 118.6 to 80.9 fractures per 100,000 person-years) and by 25.0% in males (from 68.2 to 51.1 fractures per 100,000 person-years). Joinpoint regression analysis identified a change in the linear slope around 1996. For the overall population, the average age-adjusted annual percentage decrease in hip fracture rates was 1.2% (95% confidence interval, 1.0%-1.3%) per year from 1985 to 1996 and 2.4% (95% confidence interval, 2.1%-2.6%) per year from 1996 to 2005 (P < .001 for difference in slopes). Similar changes were seen in both females and males with greater slope reductions after 1996 (P < .001 for difference in slopes for each sex). CONCLUSIONS Age-standardized rates of hip fracture have steadily declined in Canada since 1985 and more rapidly during the later study period. The factors primarily responsible for the earlier reduction in hip fractures are unknown.

Trabecular bone score: a noninvasive analytical method based upon the DXA image.

The trabecular bone score (TBS) is a gray‐level textural metric that can be extracted from the two‐dimensional lumbar spine dual‐energy X‐ray absorptiometry (DXA) image. TBS is related to bone microarchitecture and provides skeletal information that is not captured from the standard bone mineral density (BMD) measurement. Based on experimental variograms of the projected DXA image, TBS has the potential to discern differences between DXA scans that show similar BMD measurements. An elevated TBS value correlates with better skeletal microstructure; a low TBS value correlates with weaker skeletal microstructure. Lumbar spine TBS has been evaluated in cross‐sectional and longitudinal studies. The following conclusions are based upon publications reviewed in this article: 1) TBS gives lower values in postmenopausal women and in men with previous fragility fractures than their nonfractured counterparts; 2) TBS is complementary to data available by lumbar spine DXA measurements; 3) TBS results are lower in women who have sustained a fragility fracture but in whom DXA does not indicate osteoporosis or even osteopenia; 4) TBS predicts fracture risk as well as lumbar spine BMD measurements in postmenopausal women; 5) efficacious therapies for osteoporosis differ in the extent to which they influence the TBS; 6) TBS is associated with fracture risk in individuals with conditions related to reduced bone mass or bone quality. Based on these data, lumbar spine TBS holds promise as an emerging technology that could well become a valuable clinical tool in the diagnosis of osteoporosis and in fracture risk assessment.

Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: The manitoba study

The measurement of BMD by dual‐energy X‐ray absorptiometry (DXA) is the “gold standard” for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel gray‐level texture measurement that can be extracted from DXA images, correlates with 3D parameters of bone microarchitecture. Our aim was to evaluate the ability of lumbar spine TBS to predict future clinical osteoporotic fractures. A total of 29,407 women 50 years of age or older at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Health service records were assessed for the incidence of nontraumatic osteoporotic fracture codes subsequent to BMD testing (mean follow‐up 4.7 years). Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Osteoporotic fractures were identified in 1668 (5.7%) women, including 439 (1.5%) spine and 293 (1.0%) hip fractures. Significantly lower spine TBS and BMD were identified in women with major osteoporotic, spine, and hip fractures (all p < 0.0001). Spine TBS and BMD predicted fractures equally well, and the combination was superior to either measurement alone (p < 0.001). Spine TBS predicts osteoporotic fractures and provides information that is independent of spine and hip BMD. Combining the TBS trabecular texture index with BMD incrementally improves fracture prediction in postmenopausal women.

Low bone mineral density and fracture burden in postmenopausal women

Background: The study objectives were to determine fracture rates in relation to bone mineral density at various central skeletal sites, using the World Health Organization definition for osteoporosis (T-score –2.5 or less), and to contrast fracture patterns among women 50 to 64 years of age with those among women 65 years of age and older. Methods: Historical cohort study with a mean observation period of 3.2 (standard deviation [SD] 1.5) years. The study group (16 505 women 50 years of age or older) was drawn from the Manitoba Bone Density Program database, which includes all bone mineral density results for Manitoba. Baseline density measurements for the lumbar spine and hip were performed with dual-energy x-ray absorptiometry. Outcomes included the percentage of osteoporotic fractures and the rates of fracture and excess fracture (per 1000 person-years) among postmenopausal women with osteopenia and osteoporosis relative to those with normal bone mineral density (according to the classification of the World Health Organization). Results: The mean age was 65 (SD 9) years, and the mean T-scores for all sites fell within the osteopenic category. There were 765 incident fractures (fracture rate 14.5 [95% confidence interval, CI, 13.5–15.6 [per 1000 person-years). Fracture rates were significantly higher among women 65 years of age or older than among women 50–64 years of age (21.6 [95% CI 19.7–23.4] v. 8.6 [95% CI 7.5–9.7] per 1000 person-years, p < 0.001). Although fracture rates were significantly higher among women with osteoporotic T-scores, most fractures occurred in women with nonosteoporotic values (min–max: 59.7%–67.8%). Interpretation: In this study, most of the postmenopausal women with osteoporotic fractures had nonosteoporotic bone mineral density values. This finding highlights the importance of considering key clinical risk factors that operate independently of bone mineral density (such as age) when assessing fracture risk.

Type 2 diabetes and bone.

There is a growing body of research showing that diabetes is an independent risk factor for fracture. Type 2 diabetes (T2D), which predominates in older individuals and is increasing globally as a consequence of the obesity epidemic, is associated with normal or even increased dual‐energy x‐ray absorptiometry (DXA)‐derived areal bone mineral density (BMD). Therefore, the paradoxical increase in fracture risk has led to the hypothesis that there are diabetes‐associated alterations in material and structural properties. An overly glycated collagen matrix, confounded by a low turnover state, in the setting of subtle cortical abnormalities, may lead to compromised biomechanical competence. In current clinical practice, because BMD is central to fracture prediction, a consequence of this paradox is a lack of suitable methods, including FRAX, to predict fracture risk in older adults with T2D. The option of adding diabetes to the FRAX algorithm is appealing but requires additional data from large population‐based cohorts. The need for improved methods for identification of fracture in older adults with T2D is an important priority for osteoporosis research.

A meta-analysis of the association of fracture risk and body mass index in women.

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person‐years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m2) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non‐obese women. Compared to a BMI of 25 kg/m2, the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m2 was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored.

Proton-Pump Inhibitor Use Is Not Associated With Osteoporosis or Accelerated Bone Mineral Density Loss

BACKGROUNDS & AIMS Recent studies have shown an association between proton-pump inhibitor use (PPI) and hip fracture. The mechanism by which PPI use promotes the development of hip fracture is uncharacterized. Therefore, we sought to determine whether PPI use is associated with osteoporosis or accelerated bone mineral density (BMD) loss. METHODS We used the Manitoba Bone Mineral Density Database to determine the relationship between chronic PPI use and osteoporosis on an initial assessment of BMD and on BMD loss between successive assessments of BMD. In the cross-sectional study, cases with osteoporosis at the hip or lumbar vertebrae (T-score < or =-2.5) were matched to 3 controls with normal BMD (T-score > or =-1.0). In the longitudinal analysis, the change in BMD among PPI users and nonusers between successive BMD assessments was assessed. Conditional logistic regression and multivariate linear regression were used to obtain estimates of the association between PPI use and osteoporosis and of the annualized change in BMD associated with PPI use. RESULTS PPI use was not associated with having osteoporosis at either the hip (OR, 0.84; 95% CI, 0.55-1.34) or the lumbar spine (OR, 0.79; 95% CI, 0.59-1.06) for PPI use >1500 doses over the previous 5 years. In the longitudinal study no significant decrease was observed in BMD at either site attributable to PPI use. CONCLUSIONS PPI use does not appear to be associated with either the presence of osteoporosis or accelerated BMD loss. The association between PPI use and hip fracture is probably related to factors independent of osteoporosis.