Stratification of bone fracture risk in patients with celiac disease.

BACKGROUND AND AIMS: Our objective in this cross-sectional, case-control study was to gain insight into celiac osteopathy by examining a well-defined cohort of patients with a wide clinical spectrum of the disease. METHODS: We studied 148 unselected celiac patients and 296 (1:2) age- and sex-matched controls diagnosed with functional gastrointestinal disorders. Based on the clinical history, 53% were classically symptomatic, 36% had subclinical celiac disease, and 11% were silent, detected by screening. The fracture information was obtained through an in-person interview using a pre-designed questionnaire. RESULTS: Classically symptomatic patients had an increased number of fractures in the peripheral skeleton (47%) compared with age- and sex-matched controls (15%; odds ratio, 5.2; 95% confidence interval, 2.8-9.8). However, fractures in subclinical/silent celiac cases (20%) were no different from those in controls (14%; odds ratio, 1.7, 0.7-4.4). Compared with the subclinical/silent group, a significantly greater prevalence of fractures was detected in classically symptomatic patients (odds ratio, 3.6, 1.7-7.5). Compared with controls, celiac disease patients had significantly more fractures produced by mild trauma (P < 0.01), but there were no differences in the severity of trauma events that induced fractures. Mean bone density femoral neck z score was higher for subclinical/silent cases compared with classically symptomatic patients (P < 0.05). CONCLUSIONS: Celiac patients show a very wide variation in fracture risk, with increased risk in classically symptomatic patients. Diagnostic and therapeutic strategies to prevent bone loss and fracture should be preferentially used in the subgroup of patients with classic clinical disease.     

Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk

Aims/hypothesis We studied the association between fractures and type 1 and type 2 diabetes mellitus.Methods In this case-control study, all subjects diagnosed with a fracture (n=124,655) in Denmark served as cases, and for each case three control subjects (n=373,962) matched for sex and age were retrieved from the general population.Results Type 1 and type 2 diabetes were associated with an increased risk (1) of any fracture (odds ratio [OR]=1.3, 95% CI: 1.2–1.5 for type 1 diabetes and 1.2, 95% CI: 1.1–1.3 for type 2 diabetes after adjustment for confounders) and (2) of hip fractures (OR=1.7, 95% CI: 1.3–2.2 for type 1 diabetes, and 1.4, 95% CI: 1.2–1.6 for type 2 diabetes). Furthermore, type 2 diabetes was associated with a significant increase in forearm fractures (OR=1.2, 95% CI: 1.0–1.5), and type 1 diabetes was associated with an increased risk of spine fractures (OR=2.5, 95% CI: 1.3–4.6), whereas type 2 diabetes was not. Use of metformin and sulphonylureas was associated with a significantly decreased risk of any fracture, whereas a non-significant trend towards decreased risk of any fracture was associated with the use of insulin. Except for a decrease in hip fractures with use of sulphonylureas, no change in fracture risk in the hip, spine or forearm was associated with the use of insulin or oral antidiabetic drugs.Conclusions/interpretation Type 1 and type 2 diabetes are associated with an increased risk of any fracture and hip fractures. The use of drugs to control diabetes may reduce the association between diabetes and fractures.     

Celiac Disease and Lymphoma Risk: A Multicentric Case–Control Study in Spain

Celiac disease is a highly prevalent condition frequently misdiagnosed because of heterogeneity of the clinical symptoms. It is well recognized that enteropathy-associated T-cell lymphoma is an uncommon lymphoma type linked to celiac disease; it has also been suggested that other types of lymphomas may be associated with celiac disease. Our aim was to estimate the risk of all lymphoma associated with celiac disease. Serological markers and personal interviews were obtained from 298 consecutive lymphoma cases and 251 matched controls recruited in four Spanish hospitals. Celiac disease was detected in two cases (0.67%; n = 298) and in three controls (1.2%; n = 251). Treated celiac disease was observed in one patient with lymphoma and in two control subjects. In our series, there was no evidence that celiac disease was a risk factor for lymphoma (OR = 0.62, 95% CI = 0.10-3.79). Serological screening for CD is not recommended in people with lymphoma.     

Bone Mineralization in Young Patients with Type 1 Diabetes Mellitus and Screening-identified Evidence of Celiac Disease

The aims of this study were to evaluate bone mineral density (BMD) and bone turnover markers in patients with type 1 diabetes and screening-identified evidence of celiac disease, i.e., celiac autoimmunity. We screened 50 consecutive type 1 diabetic patients for IgA antitissue transglutaminase to identify those with celiac autoimmunity. Eight seropositive patients were identified on this screening, and 12 patients matched for gender and age range were selected as a control group from among the type 1 diabetic patients without celiac autoimmunity. Patients and controls underwent dual-energy X-ray absorptiometry (DEXA) for measurement of bone mineral status and had their blood levels of osteocalcin, carboxy-terminal telopeptide of type I collagen (CTX), calcium, and phosphorus determined. BMD was further adjusted for height, weight, and pubertal stage. Radiographic and blood markers of bone mineralization were compared between patients and controls. BMD (Z-score) at the lumbar spine was −1.44 ± 0.5 SD for patients and 0.04 ± 0.2 SD for controls (P = 0.02). Bone mineral content was 37.9 ± 4.5 g for patients and 49.4 ± 2.6 g for controls (P = 0.049). Adjusted BMD was −0.62 ± 0.5 SD for patients and 0.81 ± 0.09 SD for controls (P = 0.04). After adjustment, four patients and none of the controls presented BMD < −1 SD (P = 0.01). Osteocalcin, CTX, calcium, and phosphorus blood levels were not significantly different between patients and controls. Celiac autoimmunity is associated with reduced bone mineralization in type 1 diabetic patients. The pathophysiological mechanisms and clinical relevance of this finding remain to be further investigated.     

Family history and risk of type 1 diabetes mellitus

The aim of the study was to evaluate association of type 1 diabetes in children and adolescents with positive family history of type 1 diabetes, type 2 diabetes, and thyroid, adrenal, rheumatic, allergic, celiac and some other diseases. A case-control study was conducted in Belgrade. The case group comprised 105 subjects ≤ 16 years old who were for the first time hospitalized because of type 1 diabetes during the period 1994–1997. For each case, two controls were chosen among children and adolescents treated for skin diseases. Cases and controls were individually matched by age (± one year), sex and place of residence (all were from Belgrade). In the statistical analyses we used χ²-test, Fisher's exact test and univariate and multivariate logistic regressions. According to multivariate logistic regression analysis, risk of type 1 diabetes was significantly associated with a positive family history for type 1 diabetes (OR=4.04; 95% CI, 2.31–7.07), allergic diseases (OR=3.32; 95% CI, 1.63–6.76), celiac and Crohn's diseases (OR=11.02; 95% CI, 1.14–106.89) and other diseases (thrombocytopenia, alopecia areata, psoriasis, chronic uveitis and pernicious anemia; OR=3.63; 95% CI, 1.05–12.48). Received: 10 August 2000 / Accepted in revised form: 15 April 2002     

Risk of hip fracture in Addison's disease: a population-based cohort study

Abstract. Björnsdottir S, Sääf M, Bensing S, Kämpe O, Michaëlsson K, Ludvigsson JF (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; and Örebro University Hospital, Örebro; Sweden). Risk of hip fracture in Addison’s disease: a population‐based cohort study. J Intern Med 2011; 270 : 187–195. Objectives. The results of studies of bone mineral density in Addison’s disease (AD) are inconsistent. There are no published data on hip fracture risk in patients with AD. In this study, we compare hip fracture risk in adults with and without AD. Design. A population‐based cohort study. Methods. Through the Swedish National Patient Register and the Total Population Register, we identified 3219 patients without prior hip fracture who were diagnosed with AD at the age of ≥30 years during the period 1964–2006 and 31 557 age‐ and sex‐matched controls. Time to hip fracture was measured. Results. We observed 221 hip fractures (6.9%) in patients with AD and 846 (2.7%) in the controls. Patients with AD had a higher risk of hip fracture [hazard ratio (HR) = 1.8; 95% confidence interval (CI), 1.6–2.1; P < 0.001]. This risk increase was independent of sex and age at or calendar period of diagnosis. Risk estimates did not change with adjustment for type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis or coeliac disease. Women diagnosed with AD ≤50 years old had the highest risk of hip fracture (HR = 2.7; 95 % CI, 1.6–4.5). We found a positive association between hip fracture and undiagnosed AD [odds ratio (OR) = 2.4; 95 % CI, 2.1–3.0] with the highest risk estimates in the last year before AD diagnosis (OR = 2.8; 95 % CI, 1.8–4.2). Conclusion. Both clinically undiagnosed and diagnosed AD was associated with hip fractures, with the highest relative risk seen in women diagnosed with AD ≤50 years of age.     

Risk of colorectal neoplasia in patients with celiac disease: A multicenter study

Background and aimsThe association of celiac disease with colorectal neoplasia is controversial. The aim of this study was to determine the risk of colorectal neoplasia among patients with celiac disease.MethodsWe carried out a multicenter, retrospective case–control study, within four community hospitals. Celiac disease patients with a complete colonoscopy were regarded as cases and those without celiac disease as controls. For each case, two controls matched for age, sex, indication for colonoscopy and colorectal cancer family history, were randomly selected. The main outcome evaluated was risk of colorectal polyps, adenomas, advanced neoplastic lesions and cancer.ResultsWe identified 118 patients with celiac disease and 236 controls. The risk of polyps, adenomas and advanced neoplastic lesions was similar in both groups (OR 1.25, CI 0.71–2.18, p = 0.40; OR 1.39, CI 0.73–2.63, p = 0.31; and OR 1.00, CI 0.26–3.72, p = 1.00, respectively). On multivariate analysis, age > 75 years old, and first-grade CRC family history were associated with adenomas (OR 2.68 CI 1.03–6.98, OR 6.68 CI 1.03–47.98 respectively) and advanced neoplastic lesions (OR 15.03, CI 2.88–78.3; OR 6.46 CI 1.23–33.79, respectively). With respect to celiac disease characteristic, a low adherence to a gluten free diet was independently associated with the presence of adenomas (OR 6.78 CI 1.39–33.20 p = 0.01).ConclusionsCeliac disease was not associated with an increased risk of colorectal neoplasia. Nonadherence to a strict gluten free diet was associated with the presence of adenomas. Further studies addressing celiac disease characteristics are needed to confirm this observation.     

Long-term fracture risk in patients with Crohn's disease: a population-based study in Olmsted County,Minnesota

BACKGROUND & AIMS: Osteoporosis is common in patients with Crohn's disease, but less is known about their risk of actual fractures. METHODS: The medical records of all 238 Olmsted County, Minnesota, residents diagnosed with Crohn's disease between 1940 and 1993 were reviewed for evidence of subsequent fractures compared with a control group of county residents matched by age and sex. The risk ratio of fracture in patients relative to controls was estimated using the Cox proportional hazards regression model. The cumulative incidence of fracture following diagnosis was estimated using the Kaplan-Meier method. RESULTS: Sixty-three patients had 117 different fractures. The cumulative incidence of any fracture from the time of diagnosis onward was 36% at 20 years versus 32% in controls (P = 0.792). Compared with controls, the overall risk ratio for any fracture was 0.9 (95% confidence interval [CI], 0.6-1.4), whereas the relative risk for an osteoporotic fracture was 1.4 (95% CI, 0.7-2.7). The risk ratio for thoracolumbar vertebral fracture was 2.2 (95% CI, 0.9-5.5). Cox proportional hazards regression identified only age as a significant clinical predictor of fracture risk (hazard ratio per 10-year increase in age, 1.3; 95% CI, 1.1-1.5). Specifically, use of corticosteroids and surgical resection did not predict risk of fracture among these unselected patients with Crohn's disease from the community. CONCLUSIONS: In this population-based inception cohort of patients with Crohn's disease, the risk of fracture was not elevated relative to age- and sex-matched controls.     

White blood-cell count and the risk of impaired fasting glucose or Type II diabetes in middle-aged Japanese men

Aims/hypothesis: To investigate the association between white blood-cell (WBC) count and the development of diabetes, independent of cigarette smoking. Methods: We examined 2953 Japanese men who were office workers and between 35 and 59 years of age and who did not have impaired fasting glucose (IFG) (a fasting glucose concentration of 6.1–6.9 mmol/l), Type II (non-insulin-dependent) diabetes mellitus (a fasting glucose concentration of ≥ 7.0 mmol/l or more or receipt of hypoglycaemic medication), medication for hypertension, and a history of cardiovascular disease. Fasting glucose concentrations were measured at annual health examinations from May 1994 through May 2000. Results: After controlling for potential predictors of diabetes, the relative risk for IFG or Type II diabetes mellitus compared with a WBC count of less than 5.3 · 10⁹ cells/l was 1.2 (95 %-CI, 0.6–2.3), 1.6 (CI, 0.8–3.1), and 2.5 (CI, 1.2–5.1) among non-smokers (p for trend = 0.009): and 1.0 (CI, 0.4–2.5), 2.3 (CI, 1.0–5.1), and 3.1 (CI, 1.4–7.1) among ex-smokers (p for trend = 0.001) with WBC counts of 5.3–6.1, 6.2–7.2, and 7.3 · 10⁹ cells/l or more, respectively. Among current smokers, the respective multivariate-adjusted relative risks for IFG or Type II diabetes mellitus were 1.1 (CI, 0.6–2.1), 1.4 (CI, 0.8–2.4), and 1.2 (CI, 0.7–2.1) (p for trend = 0.460). Conclusion/hypothesis: Although the selection of a rigorously normoglycaemic cohort might have had an influence on these observations, higher WBC counts seem to predict the development of IFG or Type II diabetes mellitus, primarily in non-smokers. [Diabetologia (2002) 45: 42–48] Received: 16 July 2001 and in revised form: 13 September 2001     

Fracture experience of patients with coeliac disease: a population based survey

BACKGROUND: While coeliac disease is now recognised as being associated with both osteoporosis and osteomalacia, the size of any increase in the risk of fracture in patients with coeliac disease compared with the general population has not been quantified. Aim: To examine the fracture experience of adults with coeliac disease compared with the general population. SUBJECTS: Patients with coeliac disease diagnosed in adulthood and born before 1950, selected from two large population based disease registers, and age and sex frequency matched controls identified from local general practitioner lists. METHODS: A four page lifestyle and general health questionnaire which included specific questions about fracture experience. RESULTS: Analysis was performed on 244 patients with coeliac disease and 161 controls, giving response rates of 89% and 72%, respectively. Eighty two (35%) coeliac patients and 53 (33%) controls reported ever having sustained one or more fractures, giving an age and sex adjusted odds ratio of 1.05 (95% confidence interval (CI) 0.68-1.62). The most common fracture site reported was the forearm or wrist, with an adjusted odds ratio of 1.21 (95% CI 0.66-2.25) for patients with coeliac disease having had a forearm or wrist fracture. Low trauma fractures were reported by 37 patients with coeliac disease (15.7%) and by 21 controls (13.8%), with an adjusted odds ratio of 1.16 (95% CI 0.65-2.10). The risk of low trauma fracture was slightly higher in coeliac men than women (odds ratio 1.28 compared with 1.12), but this difference was not statistically significant (p=0.84). After adjustment for age, sex, body mass index, and smoking status, patients with coeliac disease reported 13% more low trauma fractures than controls (odds ratio 1.13, 95% CI 0.60-2.12). There was no difference in low trauma fracture risk before and after diagnosis of coeliac disease. CONCLUSION: No overall increased fracture risk in patients with coeliac disease was observed. Although severe osteoporosis may develop in a subset of patients, as a whole patients with coeliac disease do not represent a population at particularly high risk of osteoporotic fracture and thus targeting them for osteoporosis screening and treatment is not justified.     

Risk of fractures in celiac disease patients: a cross-sectional, case-control study

OBJECTIVES: Although osteopenia and osteoporosis are well-recognized complications of celiac disease, no controlled studies have been done to assess the prevalence of fractures in a large cohort of patients. The objectives of this study were to determine the prevalence of bone fractures and vertebral deformities in celiacs and to analyze the relationship between fractures and clinical data of patients. METHODS: We studied 165 patients with a well-established diagnosis of celiac disease. A similar number of age- and gender-matched control subjects with functional GI disorders were evaluated. The design of the study was cross-sectional, with a retrospective historical review through a personal interview of all subjects. All patients underwent bone mineral density measurement by dual-energy, x-ray absorptiometry and spinal x-ray. Vertebral deformities were determined by visual inspection of spinal x-rays and by morphometric analysis. RESULTS: Among celiacs, 41 patients (25%) referred have had from one to five fractures in the peripheral skeleton. On the contrary, only 14 (8%) control subjects experienced fractures. This difference was highly significant (odds ratio, 3.5; 95% confidence interval [CI], 1.8-7.2; p<0.0001). Although inspection of spinal x-rays showed evidence of vertebral deformities in the lumbar spine in only two patients, a more detailed examination of lateral x-rays using morphometric criteria detected lumbar spine vertebral deformities in nine (five also had fractures in the peripheral skeleton) and in four controls (odds ratio, 2.8; 95% CI, 0.7-11.5; p = NS). Eighty percent of fractures were detected before the diagnosis of celiac disease or in patients who were noncompliant with the gluten-free diet; only 7% of patients experienced fractures after starting treatment. Regression analysis adjusted for multiple comparisons showed that patients with fractures were diagnosed with celiac disease later (p<0.06) and remained undiagnosed for more prolonged periods (p<0.05). There was a trend, which did not reach statistical significance, for a lower bone mineral density in the lumbar spine and total skeleton among patients with fractures. CONCLUSIONS: This study has demonstrated that patients with celiac disease had a high prevalence of bone fractures in the peripheral skeleton. Most of these events occurred before diagnosis or while patients were noncompliant with gluten-containing diet. Our results suggest that early diagnosis and effective treatment of celiac disease were the most relevant measures to protect patients from the risk of fractures.     

Positive IgA against transglutaminase 2 in patients with distal radius and ankle fractures compared to community-based controls

Background: Patients with celiac disease (CD), including adults with subclinical disease, have low bone mineral density (BMD), deteriorated bone microarchitecture and meta-analysis show an increased risk of fracture. Immunoglobulin A (IgA) against transglutaminase 2 (IgA TG2) is a highly reliable marker to detect CD.

Main objective: To explore the prevalence of positive IgA TG2 and CD in patients with distal radius and ankle fracture compared to community-based controls.

Methods: Four hundred patients aged 40 years or above with distal fractures were included in a case–control study. About 197 controls were identified from the National Population Registry, those included had never suffered a fracture. BMD was measured, and comorbidities, medications, physical activity, smoking habits, body mass index (BMI) and nutritional factors were registered. Blood analysis to detect common causes of secondary osteoporosis was performed.

Results: About 2.5% of the fracture patients had positive IgA TG2, compared to 1% in the control group. The odds ratio, adjusted for sex and age, of having positive IgA TG2 was 2.50 (95% CI 0.54–11.56).

Conclusions: There were no significantly increased odds of CD in adult patients with fractures compared to controls; however, results imply that positive IgA TG2 is more prevalent in fracture patients than in controls. This study indicates that universal screening for CD in fracture patients is not warranted, but supports current clinical practice in Norway to suspect and investigate for CD in patients with fracture, osteoporosis and other risk factors for CD.     

A prospective study of antituberculous drug-induced hepatotoxicity in an area endemic for liver diseases

Purpose   Identification of risk factors associated with antituberculosis drug-induced hepatotoxicity (anti-TB-DIH) is important, especially in endemic area for TB and liver disease. This study assessed the incidence and risk factors of anti-TB-DIH in upper Egyptian patients treated for active pulmonary and extra-pulmonary TB. Methods  A total of 100 consecutive TB patients were prospectively followed up both clinically and biochemically before and during their course of anti-TB therapy with daily doses of isoniazid, rifampin, ethambutol, and pyrazinamide, or streptomycin. Results  Anti-TB-DIH developed in 15 (15%) patients within 15–60 days (median: 30 days) from the onset of therapy. Liver function normalized in 10 (60%) patients within 2 weeks from cessation of therapy. No recurrence of DIH was observed after reintroduction of therapy. Only 1 patient died from fulminant hepatic failure despite discontinuation of all anti-TB drugs. By univariate analysis, patients with anti-TB-DIH had more pre-existing liver disease (P = 0.024; OR: 3.60; 95% CI: 1.16–11.18), lower body mass index (BMI; P = 0.037; OR: 3.73; 95% CI: 1.04–10.56), lower serum albumin (P = 0.035; OR: 3.31; 95% CI: 1.04–10.56), and more extensive disease (P = 0.033; OR: 3.50; 95% CI: 1.11–11). Age, gender, raised baseline transaminases level, inclusion of pyrazinamide, and inactive hepatitis B or C carrier state were not significant risk factors of DIH. Using multivariate regression analysis, only pre-existing liver disease and lower BMI of 20 kg/m² or less were independent predictors of DIH (P = 0.024 and P = 0.047, respectively). Conclusion   Anti-TB-DIH is not uncommon, needs early recognition and treatment, and is more in patients with pre-existing liver disease and low BMI.     

Diabetic peripheral neuropathy is highly associated with nontraumatic fractures in Korean patients with type 2 diabetes mellitus

Objective Patients with type 2 diabetes mellitus are at greater risk of bone fractures than nondiabetics. However, the risk factors for fractures in patients with diabetes have not been fully evaluated. This study was designed to evaluate the relative frequency of fractures at different sites and the diabetes‐associated factors that affect nontraumatic bone fracture in patients with type 2 diabetes. Patients and design This retrospective case–control study recruited 144 patients with type 2 diabetes, who presented with nontraumatic fractures between March 2004 and March 2009 and 150 age‐, gender‐, body mass index (BMI)‐ and duration of diabetes‐matched control subjects. Nontraumatic fractures were confirmed using patients’ medical records and radiological findings. All subjects were examined for their diabetes status and associated factors for fracture, including bone mineral density (BMD). Results Of 150 reported bone fractures, the hip was the most frequent fracture site (32·7%), followed by the upper extremity (19·3%). Nontraumatic fractures were associated with diabetic retinopathy, diabetic peripheral neuropathy, stroke history, previous fracture and insulin treatment (P < 0·05). In multivariate analyses, independently associated factors for bone fracture were diabetic peripheral neuropathy [odds ratio (OR) = 37·3, 95% confidence interval (CI) = 1·46–652·57] and previous fracture (OR = 9·54, 95% CI = 1·18–77·37; P < 0·05). Conclusions The hip was the most frequent site of nontraumatic fracture, and diabetic peripheral neuropathy was significantly associated with an increased risk of nontraumatic fractures in patients with type 2 diabetes.     

Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trøndelag Health Survey

Abstract Aims/hypothesis. To study if people with Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus have increased risk of hip fracture. Methods. The study population consisted of 35 444 people 50 years of age and older, attending a health screening in a Norwegian county. They were followed up with respect to hip fracture for 9 years, and 1643 new hip fractures were recorded. Results. The relative risk of hip fracture for women with Type I diabetes compared with women without diabetes was 6.9 (95 % confidence interval 2.2–21.6) adjusted for age, body mass index and daily smoking. The relative risk for men was nearly the same, but not statistically significant. Among women 50–74 years of age with Type II diabetes for more than 5 years, the relative risk was 1.8 (95 % confidence interval 1.1–2.9). This increased risk persisted when insulin-treated women were excluded from the analysis. After additional adjustment for possible medical consequences of diabetes (impaired vision, impaired motor abilities and history of stroke) the relative risk among women 50–75 years of age with Type II diabetes was reduced to 1.5 (95 % confidence interval 0.9–2.5). Conclusion/interpretation. We found an increased risk of hip fracture in women younger than 75 years with Type I diabetes or with Type II diabetes of long duration. In older men, there was an increased risk associated with Type II diabetes of shorter duration. Whether the increased risk is attributed to reduced bone mass or to factors associated with falling has not been determined. [Diabetologia (1999) 42: 920–925] Received: 4 January 1999 and in revised form: 29 March 1999     

Lactose intolerance: a risk factor for reduced bone mineral density and vertebral fractures?

Background: The purpose of the present study was to determine differences, if any, in bone mineral density, the risk of fracture, and clinical behavior in patients with lactose intolerance investigated by hydrogen breath test. Methods: The study population (n = 218; age, mean ± SD, 58.2 ± 11.5 years) consisted of 103 healthy individuals negative hydrogen breath test (ΔH2 0–20 ppm; group I), and 115 individuals with evidence of lactose intolerance according to the hydrogen breath test (ΔH2 > 20 ppm), of whom 40 individuals had test results of 20 ppm < ΔH2 < 59 ppm (group II). The remaining 75 individuals were strongly positive on the hydrogen breath test (ΔH2 > 60 ppm; group III). The entire study population was measured for bone mineral density in the nondominant forearm and in the vertebra (quantitative computed tomography [qCT]). Radiographs of the spine were studied for fractures. Results: In healthy individuals, bone mineral density in the vertebra assessed by qCT (mean ± SD, 111.2 ± 31 mg/cc) did not significantly differ between those with mild (qCT, mean ± SD, 109.8 ± 35 mg/cc) and those with severe (qCT, mean ± SD, 107.7 ± 36 mg/cc) lactose intolerance. Lactose-intolerant individuals had more vertebral fractures per patient when compared with those with mild lactose intolerance or controls (P < 0.05). Considering vertebral and self-reported nonvertebral fractures, no statistically significant differences were found. In the entire group, the overall occurrences of fracture in the presence of lactose intolerance and in controls were comparable after correction for age and body mass index (BMI). Conclusions: Individuals with lactose intolerance verified by the hydrogen breath test appear not to be at risk for accelerated bone loss. Nevertheless, a relationship between vertebral fractures and an apparent lactose intolerance cannot be excluded, as a few individuals with severe lactose intolerance had a large number of vertebral fractures. Received: December 13, 2001 / Accepted: May 17, 2002     

Radiographic measure of aorta calcification is a site-specific predictor of bone loss and fracture risk at the hip

OBJECTIVE: To investigate whether aorta calcification (AC) - a surrogate marker of atherosclerosis - is an independent indicator of low bone mass density (BMD), accelerated bone loss, and risk of future fractures in postmenopausal women. DESIGN: A prospective epidemiological study. Follow-up period was 7.5 years. SETTING: Community-based sample followed by a research institute. SUBJECTS: A total of 2662 generally healthy postmenopausal women with a mean age of 65.0 +/- 7.1 years at baseline. MAIN OUTCOME MEASURES: Annual rate of changes in BMD (DEXA) and AC (X-rays), vertebral fractures (X-rays), hip fractures (questionnaire). RESULTS: Advanced AC at baseline was significantly associated with lower BMD and accelerated bone loss from the proximal femur. In a multivariate logistic regression model, age (OR 1.1, 95% CI 1.0-1.2, P = 0.02), body mass index (BMI; OR 0.9, 95% CI 0.8-1.0, P = 0.03) and the severity of AC (OR 2.3, 95% CI 1.1-4.8, P = 0.03) were independent predictors of hip fractures. Adjusted OR for vertebral fracture was 1.2 (95% CI 1.0-1.5, P = 0.12). CONCLUSIONS: Aorta calcification seems to independently contribute to the development of osteoporosis in the proximal femur. Further studies are needed to clarify whether effective atherosclerosis prevention lowers hip fracture risk.     

Fractures in patients with primary idiopathic hypothyroidism.

AIM: To study fracture risk and risk factors for fractures in patients with primary idiopathic hypothyroidism (ICD 10: E03.9). DESIGN: Historical follow-up. MATERIAL AND METHODS: A self-administered questionnaire was issued to 628 patients with primary idiopathic levothyroxine-substituted hypothyroidism. A total of 412 (65.6%) responded and of these, 408 could be analyzed. The 408 respondents were age- (+/- 5 years) and gender-matched with 408 normal controls randomly selected from the background population who responded to the same questionnaire. RESULTS: Overall fracture risk was increased in patients compared to controls (relative risk: RR = 1.6, 95% CI: 1.0-2.5). However, the increase was temporary and limited to the period within the first 2 years after the diagnosis of hypothyroidism (RR = 3.1, 95% CI: 1.4-7.0). Before the diagnosis and more than 2 years after the diagnosis, the fracture risk in patients did not deviate from that of the controls. The increase in fracture risk was only significant in the age group above 50 years (RR = 1.8, 95% CI: 1-3.2), and was limited to the forearms (RR = 3.0, 95% CI: 1.4-6.3 for the entire patient population). CONCLUSIONS: There was a temporary increase in fracture risk within the first 2 years after diagnosis of primary idiopathic hypothyroidism. The fracture risk was mainly increased in the age group above 50 years, and the increased risk was limited to the forearms.