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Introduction The biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis. Methods This case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n = 66, mean age 68.2 ± 8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n = 54, mean age 67 ± 9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17β-estradiol levels by radioimmunoassay based on ultrasensitive methods. Results In the ARs group, sclerostin serum levels were significantly lower ( p = 0.02) and estradiol concentrations significantly higher ( p = 0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38–82.79, p = 0.004) and sclerostin levels (OR 1.11, 95% CI 1.02–1.20, p = 0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure. Conclusions Sclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis.

Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density (BMD) to evaluate the probability of Colles' fracture. Two-hundred eighty-nine postmenopausal women (62.3 +/- 8.7 yr) with (n = 76) and without (n = 213) Colles' fracture were studied. BMD of lumbar spine and proximal femur was evaluated in all women by dual-energy X-ray absorptiometry (DXA) and speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness in the calcaneus were measured by a Sahara ultrasonometer (Hologic). Patients suffering from Colles' fracture had lower values of BMD adjusted by height at the lumbar spine, L2-L4 (0.797 g/cm2 vs 0.860 g/cm2), femoral neck (0.685 g/cm2 vs 0.712 g/cm2 ), SOS (1518 m/sg vs 1525 m/sg), and stiffness (74.6 vs 77.7) (p0.05). Nevertheless, BUA values were similar in both groups. After stepwise logistic regression analysis, the area found under receiver operating characteristic (ROC) curves was 0.60 for L2L4 and 0.63 for a formula combining L2L4 and height. Our data suggest that patients suffering from Colles' fracture have lower values of BMD by DXA, SOS, and stiffness. However, the ability of these techniques to discriminate is low because the values for the area under ROC curve are 0.60 for L2-L4 and 0.63 for a formula derived of the combination of L2-L4 and height.

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross-sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti-osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual-energy X-ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx™) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47–8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55–9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93–0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem. © 2012 American Society for Bone and Mineral Research.

An association between cardiovascular disease and osteoporosis is described. A number of drugs often used by patients with coronary heart disease, such as thiazides, statins and beta-blockers, have shown controversial effects on bone. 1) To study the possible association between coronary heart disease (CHD) and bone mass density (BMD), quantitative ultrasound measurements (QUS) and the prevalence of fragility and vertebral fractures. 2) To study the possible influence of a number of drugs, statins, thiazides and beta-blockers, on BMD and fractures.Case-control study performed on 74 postmenopausal women who had recently suffered from CHD, and 111 age-matched controls. BMD was measured by Dual X-Ray Absorptiometry (DXA) at the lumbar spine and proximal femur. Quantitative Ultrasound (QUS) was also measured at the heel. Vertebral fractures were diagnosed by lateral, thoracic and lumbar X-rays. The occurrence of non-vertebral fractures was determined by examination of medical records.Patients with CHD had higher values of BMI. They had a higher prevalence of arterial hypertension and hyperlipidemia, and consequently higher consumption of beta-blockers and statins, but not of thiazides, and had lower alcohol consumption. Patients with CHD had higher BMD values, measured by DXA at the proximal femur, than controls, but there were no differences in DXA values at the lumbar spine or QUS at the heel between the two groups. The prevalence of all fragility factures was slightly higher in patients with CHD, but not to a significant extent. The prevalence of vertebral fractures was similar in the two groups. In a logistic analysis to identify factors associated with all fractures, beta-blockers were positively associated with fragility fractures, and DXA at the femoral neck was inversely associated with fragility fractures.Postmenopausal women with CHD have higher values of BMD at the proximal femur but, despite this, show a slight but non-significant increase in the prevalence of fragility fractures. Beta-blockers are independently associated with fragility fractures, but thiazides and statins are not.

Background and aims: Type 2 diabetes mellitus (DM) has a high prevalence in aging obese postmenopausal women. It is not clear whether or not diabetes produces an increase in bone mineral density or an increase in fracture rates. Objective: The main objective of this study was to investigate whether type 2 DM produces a higher prevalence of vertebral, hip and non-vertebral fractures in obese postmenopausal Caucasian women. A secondary objective was to study the influence of DM in quantitative ultrasound measurements of the heel (QUS) and bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA), in both lumbar spine (L2–L4) and proximal femur. Method: This study was a prospective cohort of 111 patients with type 2 DM and 91 control individuals (CTR) over age 65 and obese, recruited from 16 centers in Spain. Main Outcome Measures: Lateral dorsal and lumbar X-rays were performed to assess vertebral fractures. Hip and non-vertebral fractures were noted from medical records, written reports or X-ray studies. QUS measurements were made of the calcaneus and BMD measurements of the lumbar spine (L2–L4) and proximal femur. Results: Patients had higher BMD in the lumbar spine (L2–L4) than controls (0.979 g/cm2 vs 0.927 g/cm2, p=0.035), but we found no statistically significant differences in the proximal femur. QUS measurements showed similar values in both groups: BUA (69.3 dB/Mhz vs 66.7 dB/Mhz, p=0.291), SOS (1537 m/sg vs 1532 m/sg, p=0.249) and QUI (87.5 vs 83.7, p=0.153). No statistically significant differences were found in any case. There was no association between vertebral, hip and non-vertebral fractures and DM. The crude odds ratio, without adjusting was 1.045 (CI 957o 0.531; 2.059), and the adjusted odds ratio was 0.927 (CI 95% 0.461; 1.863). Conclusions: In obese postmenopausal Caucasian women, type 2 DM produces an increase in BMD of the lumbar spine without changes in BMD of the proximal femur or in QUS measurements of the heel. The prevalence of vertebral, hip and non-vertebral fractures did not increase in type 2 DM.

Introduction Epidemiological studies in Europe have revealed that the prevalence of Paget's disease of bone (PDB) has marked geographic variations. At present, the prevalence of PDB in Spain is unknown, limited to data from isolated towns or centers. We conducted a radiological national-based survey, to estimate the age and sex prevalence of PDB and its geographic variation within the country. In addition, we tested the patients' awareness of their disease. Methods Stratified samples throughout Spain of abdominal radiographs, of subjects aged ≥ 55 years, from stored consecutive digitalized films in selected hospitals were obtained, over the period of 2006–2007. Radiographs including all lumbar vertebrae, pelvis, sacrum and femoral heads were examined for the diagnosis of PDB, according to standardized criteria. Age, sex and information regarding patient's awareness of the illness were obtained from the hospital files. Results A total of 4528 radiographs from 13 centers were evaluated. The crude prevalence of PDB was 1% (95%CI: 0.7–1.3) in individuals older than 55, and the estimated prevalence ranged from 1.1% (95%CI: 0.8–1.4) to 1.6% (95%CI: 1.1–2.1) when a reported pelvic involvement in 60–90% of PDB patients was considered. The prevalence was slightly higher in men than in women, and significantly higher in individuals older than 75. A significant geographic variation in prevalence was observed within the country ( p = 0.004). 73% of PDB patients were unaware of their illness at the time of the radiological survey. Conclusions Prevalence of PDB in Spain is at least 1% in individuals older than 55, with remarkable geographical variations and age related differences. Most patients were unaware of their disease.

Background: The treatment of osteoporosis among postmenopausal women represents a major public health challenge because long-term therapy is needed to prevent fractures and chronic disability. Low patient compliance with prescribed osteoporosis treatments can severely distort the validity of controlled clinical trials. Raloxifene and alendronate have been shown to reduce the incidence of osteoporotic fracture in postmenopausal women in well-conducted randomized trials, but few data are available on the rate of adherence to these treatments in routine clinical practice. Objective: The primary aim of this study was to assess the compliance of postmenopausal women at risk for osteoporotic fractures who were treated with raloxifene hydrochloride (RLX) versus alendronate sodium (ALN) during a 12-month observational period in a routine clinical setting. Secondary objectives were the assessment of factors that might contribute to noncompliance and patient satisfaction. Methods: This open-label, prospective, multicenter, nonrandomized, observational, comparative study was conducted at 154 centers across Spain. Assignment to either RLX or ALN treatment was determined by the physician and was based on each patient's clinical profile. Compliance with RLX (60-mg tablet once daily) versus ALN (10-mg tablet once daily) was assessed using 3 different compliance assessment tools: the Morisky-Green test, the Autocompliance test, and the Compliance Questionnaire. A logistic regression model was used to assess different factors affecting compliance. Patient satisfaction was also assessed using a questionnaire. Adverse events (AEs) were collected as reasons for discontinuation in the Compliance Questionnaire and at the discontinuation visit. Results: A total of 902 women (RLX group, n = 476; ALN group, n = 426) were included in the study (mean age, 64.4 [6.9] years). Overall, patients in the RLX group reported significantly better compliance than patients in the ALN group, as collected either by the Morisky-Green test (68.7% vs 54.0%; P < 0.001) or the Autocompliance test (94.7% vs 90.6%; P = 0.033). More patients discontinued treatment prematurely in the ALN group compared with the RLX group (25.8% vs 16.4%; P < 0.001). The age-adjusted relative risk for discontinuation was 1.4-fold higher for women treated with ALN than for those treated with RLX (95% CI, 1.21-1.61). The main reason for premature discontinuation was due to AEs (RLX 4.8% vs ALN 11.0%; P < 0.001). The proportion of patients with gastrointestinal AEs was 9.9% in the ALN group and 3.4% in the RLX group (P < 0.001). Only treatment and type of physician were independent covariates of treatment compliance. After 12 months of observation, significantly more patient in the RLX group were satisfied or very satisfied with their treatment than patients in the ALN group (P < 0.001). Conclusion: In this study of postmenopausal women at risk for osteoporotic fractures, compliance with 12-month treatment with daily RLX was higher than with daily ALN in clinical setting. RLX showed significant benefits compared with ALN in terms of compliance assessed by means of the Morisky-Green and Autocompliance tests and the patients' self-reported satisfaction.