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a b s t r a c t Paget’s disease of bone is the paradigm of bone focal distortion with accelerated bone turnover. Over the years, a number of different drugs have been used to control its activity but, since biphosphonates were introduced for the treatment of the disease, they have become the preferred treatment. This review will update the therapeutic indications, available drugs and therapeutic response monitoring.

Objective Due to increasing improvement in the diagnosis, evaluation and management of osteoporosis and the development of new tools and drugs, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and other health professionals involved in the treatment of patients with osteoporosis. Methods Recommendations were developed following a nominal group methodology and based on a systematic review. The level of evidence and the degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Evidence from previous consensus and available clinical guidelines was used. Results We have produced recommendations on diagnosis, evaluation and management of osteoporosis. These recommendations include the glucocorticoid-induced osteoporosis, premenopausal and male osteoporosis. Conclusions We present the SER recommendations related to the biologic therapy risk management.

Resumen Objetivo Dado el creciente avance en el diagnostico como evaluacion y tratamiento de la osteoporosis, y la incorporacion de nuevas herramientas y medicamentos, desde la Sociedad Espanola de Reumatologia (SER) se ha impulsado el desarrollo de recomendaciones basadas en la mejor evidencia posible. Estas deben de servir de referencia para reumatologos y otros profesionales de la salud implicados en el tratamiento de pacientes con osteoporosis. Metodos Las recomendaciones se emitieron siguiendo la metodologia de grupos nominales. El nivel de evidencia y el grado de recomendacion se clasificaron segun el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por tecnica Delphi. Se utilizo toda la informacion de consensos previos y guias de practica clinica disponibles. Resultados Se realizan recomendaciones sobre el diagnostico, la evaluacion y el tratamiento en pacientes con osteoporosis. Estas recomendaciones incluyen la osteoporosis secundaria a glucocorticoides, la osteoporosis premenopausica y la del varon. Conclusiones Se presentan las recomendaciones SER sobre el diagnostico, la evaluacion y el manejo de pacientes con osteoporosis.

Resumen Objetivo Describir las caracteristicas clinicas y epidemiologicas de los sujetos incluidos en el Registro Nacional de Paget. Sujetos y metodo Registro de pacientes con enfermedad osea de Paget (EOP), confirmada radiologicamente, de 25 centros participantes. Se recogieron datos clinicoepidemiologicos (edad, sexo, fecha y manifestaciones al diagnostico y tratamientos), calidad de vida (CV) (cuestionario EuroQol de 5 dimensiones), estado de salud, factores ambientales (profesion, antecedentes de sarampion, contacto con animales, consumo de lacteos, condiciones de la vivienda, lugar de nacimiento y domicilio) y familiares (historia de EOP, procedencia de los ascendientes y numero de hijos). Se realizo una descripcion estadistica de los datos. Resultados El registro incluyo a 602 sujetos con edad media de 62 ± 11 anos con predominio de varones (55%). El 79% de los sujetos presentaba sintomas en el momento del diagnostico, fundamentalmente dolor (83%). El 82% de los sujetos habia recibido tratamiento, principalmente bisfosfonatos, con mas de un farmaco en el 47% de los casos. A pesar del tratamiento, una proporcion importante tenia limitacion de la CV, especialmente relacionada con dolor (64%), movilidad (47%) y ansiedad junto con malestar (33%). La mayor parte de los sujetos habian estado expuestos a situaciones que se consideran factores de riesgo. El 14% de los sujetos tenia historia familiar de EOP y el 1,5% de los sujetos tenia hijos con EOP. Los ascendientes de los casos familiares procedian con mas frecuencia de Avila, Salamanca, Malaga y La Coruna. Conclusiones El dolor y la limitacion de la movilidad disminuyen la CV del sujeto con EOP a pesar del tratamiento. Son frecuentes los antecedentes de exposicion a factores de riesgo.

a b s t r a c t Objectives: To describe the clinical and epidemiological characteristics of patients included in the National Register of Paget's disease. Methods: A Register of patients with Paget disease (PD), radiologically confirmed, and pertaining to 25 hospitals was analyzed. Clinical and epidemiological data were collected, including age, sex, date, and presentations at time of diagnosis, treatment, quality of life (QL) (EuroQol 5D) and perceived health, environmental factors (profession, history of measles, contact with animals, dairy consumption, housing conditions, place of birth and address) and family history (PD history, origin of the ancestors, number of children). We conducted a statistical description of the data. Results: The register included 602 patients with an average age of 62 (11) years and a predominance of male (55%). Of the patients included, 79% showed symptoms at the time of diagnosis, mainly pain (83%); 82% had received treatment, mainly bisphosphonates (47% more than one drug). Despite treatment, a significant proportion had limitations in their QL, especially related to pain (64%), mobility (47%), and anxiety/depression (33%). Most of the patients had been exposed to situations which were considered as risk factors. Of the patients included, 14% had family history of PD and 1.5% had children with PD. The ancestors of the familial cases came more frequently from Avila, Salamanca, La Coruna, and Malaga. Conclusions: The pain and the limitation of mobility decrease the QL of patients with PD despite treatment. Frequently, patients have a history of exposure to risk factors

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.

Strontium (Sr), chemical element number 38, has a content in normal diets of 0.022-0.046 mmol/day and its physiological levels are between 0.11-0.31 mmol/l. Its behaviour is similar to that of calcium. It is distributed in plasma, extracellular liquid, soft tissues and skeleton. It binds to serum proteins and is eliminated through urine and faeces. If administered alone, 25-30% is absorbed and this absorption is diminished if it is administered with calcium or food. Although absorbed both actively and passively, active absorption is vitamin-D dependent. As a divalent cation, Sr is not metabolized. In studies carried out with animals, it was shown not to have toxic effects on bone cells or on mineralization, if the doses are less than 1% of the diet (low dose ≤ 4 mmol Sr/Kg/day). A high dose of Sr induces skeletal abnormalities (rickets, mineralization defects) especially in animals with a calciumpoor diet. In studies performed, Sr inhibits bone resorption and increases the replication of pre-osteoblastic cells and secondarily the synthesis of collagen matrix. Strontium ranelate (rSr) comprises an organic part (ranelic acid) and two atoms of strontium, is absorbed orally and its absolute bioavailability is 20-25%. Sr binds little to proteins and has a great affinity for bone tissue. rSr has “in vitro” effects on bone cells, increasing DNA synthesis and the synthesis of collagen and non-collagen proteins. rSr inhibits bone resorption as it diminishes the differentiation of pre-osteoclasts and increases the replication of pre-osteoblastic cells, thus increasing bone formation. The Phase II studies with different doses of rSr versus placebo, in order to assess the dose and side effects, it can be summarized by saying that the minimum effective dose of rSr to prevent serious bone loss is 1 g/day and a dose of 2 g/day offers the best combination of efficacy. Two Phase III placebo-controlled studies conducted with 2 g/day of rSr, one into the prevention of vertebral fractures (SOTI) and the other into peripheral fractures (TROPOS), have found vertebral fractures to be reduced by 49% in the first year and by 41% after three years, with BMD increased by +6.8% and +8.1%, already adjusted, versus the baseline values and placebo, respectively. With respect to non-vertebral fractures (TROPOS) in women at high risk of fractures (women ≥ 74 years of age and femoral neck BMD of T ≤ -3), it is associated with a 36% reduction in the risk of hip fractures. The increase, compared with baseline values and placebo respectively, is +2.85% and +4.1% in femoral neck BMD and +3.58% and +4.9% in total hip, all figures also corrected. Bone alkaline phosphatase is increased and C-telopeptide diminished. Adverse events were scant and the most frequent was diarrhoea (6.1%), which disappeared after the first three months. rSr induces to the reduction in vertebral and non-vertebral fractures, is well tolerated and can be a useful therapy for the prevention of osteoporotic fractures in women with osteoporosis.

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.

Paget's disease of bone is the paradigm of bone focal distortion with accelerated bone turnover. Over the years, a number of different drugs have been used to control its activity but, since bisphosphonates were introduced for the treatment of the disease, they have become the preferred treatment. This review will update the therapeutic indications, available drugs and therapeutic response monitoring.

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 It is a matter of controversy whether or not Colles' fracture is an osteoporotic fracture. Indeed, the usefulness of quantitative ultrasound in distinguishing Colles' fracture from normal fractures is also unclear. Methods A cross-sectional case-control study was done on 469 postmenopausal Spanish women, 121 with Colles' fracture and 348 controls. Assessment of risk factors for osteoporosis and measurement of calcaneus quantitative ultrasound were carried out using a Sahara ®, Hologic ® device. Results Patients with Colles' fracture had BUA, SOS, and QUI values that were similar to those of controls, and no statistically significant differences were found. We estimated ROC curves for SOS and a score based on a linear combination of height and SOS (SH-Score). The areas under both curves were 0.56 and 0.61, respectively, which was statistically significant. To obtain 5% false-negative and 10% false-positive figures, the T-score cut-off for SOS was − 2.45 and − 0.045, respectively. Of these, only 9.2% were classified as high risk and 11% as low risk with 79.8% undetermined. Conclusions Patients with Colles' fracture had BUA, SOS, and QUI values that were similar to those of controls. Nevertheless, ROC curves calculated by a combination of height and SOS showed that quantitative calcaneus ultrasound may be a useful tool for identifying postmenopausal women with Colles' fracture. These results indicate that measuring bone mineral density with ultrasound only captures limited aspects of the pathophysiology of Colles' fractures.

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.

Background: Nail bed capillaroscopy represents a simple and innocuous diagnosis method, used in vasculitis or collagen diseases. In Fabry disease (FD), there is a vasculopathy due to the storage of globotriaosylceramide. This is the first series that studies capillaroscopy in FD. Objective: To describe and evaluate the capillary findings in Fabry patients. Materials and Methods: Eight Fabry patients were selected; five were under enzyme replacement therapy (ERT) with agalsidase-A. Results: In three patients (under ERT), the capillaroscopy showed no abnormalities; two patients had absence of some capillaries (one with ERT); in three (one with ERT) the capillaroscopy revealed ramification of capillaries. Patients with normal capillaroscopy had no symptom of acroparesthesia for more than a year. Conclusions: Capillaroscopy is a good method to evaluate small vessels in FD and seems to have a correlation with ERT benefits, clinical manifestations and capillary findings. We purpose to use the capillaroscopy in the study of Fabry patients.