Health-related quality of life of X-linked hypophosphatemia in Spain.

BACKGROUND: Health-related quality of life (HRQoL) of patients with X-linked hypophosphatemia (XLH) is lower than that of both the general population and the patients with other chronic diseases, mainly due to diagnostic delay, treatment difficulties, poor psychosocial support, and problems with social integration. Early diagnosis and optimal treatment are paramount to control the disease in patients with XLH, avoid complications, and maintain or improve their HRQoL. We, therefore, analyzed the HRQoL of pediatric and adult patients with XLH treated with conventional therapy in Spain. RESULTS: We used several versions of the EuroQol-5 dimensions (EQ-5D) instrument according to the age of patients with XLH. Then we compared the HRQoL of patients to that of the general Spanish population. Children with XLH (n = 21) had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). Adults with XLH (n = 29) had lower HRQoL, with problems in walking (93%, with 3.45% unable to walk independently), some level of pain (86%, with 3.45% experiencing extreme pain), problems with their usual activities (80%) and self-care (> 50%), and reported symptoms of anxiety and/or depression (65%). There were important differences with the general Spanish population. CONCLUSIONS: XLH impacts negatively on physical functioning and HRQoL of patients. In Spanish patients with XLH, the HRQoL was reduced despite conventional treatment, clearly indicating the need to improve the therapeutic approach to this disorder.

X-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affectingX-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affecting bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.

Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group.

The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. INTRODUCTION: The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. METHODS: The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation's Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. RESULTS AND CONCLUSION: The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.

Profile of patients who consult with internists for an osteoporosis assessment: The OSTEOMED registry.

BACKGROUND AND OBJECTIVES: Osteoporosis is considered a generalised skeletal disorder in which there is impaired bone resistance, which predisposes the individual to a greater risk of fracture. The aim of this cross-sectional study was to collect and present data on the main clinical characteristics of patients who consult medical internists in Spain. Understanding these characteristics can help in implementing action plans to improve these patients' care more effectively and efficiently. MATERIAL AND METHODS: Through an analysis of the Osteoporosis in Internal Medicine (OSTEOMED) registry, this study presents the main clinical characteristics of patients with osteoporosis who attended internal medicine consultations in 23 Spanish hospital centres between 2012 and 2017. We analysed the reasons for the consultations, the densitometric values, the presence of comorbidities, the prescribed treatment and other lifestyle-related factors. RESULTS: In total, 2024 patients with osteoporosis were assessed (89.87% women, 10.13% men). The patients' mean age was 64.1±12.1 years (women, 64.7±11.5 years; men, 61.2±14.2 years). There was no significant difference between the sexes in their history of recent falls (9.1% and 6.7%); however, there were significant differences in the daily intake of calcium from milk products (553.8±332.6mg for women vs. 450.2±303.3mg for men; p<.001) and in the secondary causes of osteoporosis (13% of men vs. 6.5% of women; p<.001). In the sample, there were 404 fractures (20%), with a notable number of confirmed vertebral fractures (17.2%, 35.6% in men vs. 15.2% in women; p<.001). A large portion of the patients did not undergo the indicated treatment and presented low levels of physical activity and sun exposure. A significant percentage of the patients presented associated comorbidities, the most common of which were hypertension (32%) and dyslipidaemia (28%). CONCLUSIONS: These results define the profile of patients with osteoporosis who attend internal medicine consultations in Spain. The results also show the multisystemic character of this condition, which, along with its high prevalence, determine that the specific internal medicine consultations dedicated to managing the condition are the appropriate place for caring for these patients.

Perfil de los pacientes que acuden al médico internista para valoración de osteoporosis: registro OSTEOMED / Profile of patients who visit medical internists for an osteoporosis assessment: The OSTEOMED registry

Antecedentes y objetivo La osteoporosis se considera un trastorno generalizado del esqueleto en el que existe una alteración de la resistencia ósea que predispone a la persona a un mayor riesgo de fractura. Este estudio transversal pretende recoger y presentar las principales características clínicas de los pacientes que acuden a la consulta de los médicos internistas en España. Conocer estas características podría facilitar la puesta en marcha de planes de actuación para mejorar la atención de estos pacientes de manera más eficaz y eficiente. Material y métodos A través del análisis del registro OSTEOMED (Osteoporosis en Medicina Interna), este trabajo presenta las principales características clínicas de los pacientes con osteoporosis que acudieron a las consultas de Medicina Interna en 23 centros hospitalarios españoles entre 2012 y 2017. Se han analizado los motivos de consulta, los valores densitométricos, la presencia de comorbilidades, el tratamiento prescrito y otros factores relacionados con el estilo de vida. Resultados En total se evaluó a 2.024 pacientes con osteoporosis (89,87% mujeres, 10,13% hombres). La edad media de los pacientes fue de 64,1 ±12,1 años (mujeres, 64,7 ±11,5 años; hombres, 61,2 ±14,2 años). No hubo diferencia entre sexos en la historia de caídas recientes (9,1-6,7%), mientras que sí se apreció en la ingesta diaria de calcio de lácteos (553,8 ±332,6mg en mujeres vs. 450,2 ±303,3mg en hombres; p <0,001) y en causas secundarias de osteoporosis (13% de hombres vs. 6,5% de mujeres; p <0,001). En la muestra se observaron un total de 404 fracturas (20%) (AU)

Background and objectives Osteoporosis is considered a generalised skeletal disorder in which there is impaired bone resistance, which predisposes the individual to a greater risk of fracture. The aim of this cross-sectional study was to collect and present data on the main clinical characteristics of patients who consult medical internists in Spain. Understanding these characteristics can help in implementing action plans to improve these patients’ care more effectively and efficiently. Material and methods Through an analysis of the Osteoporosis in Internal Medicine (OSTEOMED) registry, this study presents the main clinical characteristics of patients with osteoporosis who attended internal medicine consultations in 23 Spanish hospital centres between 2012 and 2017. We analysed the reasons for the consultations, the densitometric values, the presence of comorbidities, the prescribed treatment and other lifestyle-related factors. Results In total, 2024 patients with osteoporosis were assessed (89.87% women, 10.13% men). The patients’ mean age was 64.1±12.1 years (women, 64.7±11.5 years; men, 61.2±14.2 years). There was no significant difference between the sexes in their history of recent falls (9.1% and 6.7%); however, there were significant differences in the daily intake of calcium from milk products (553.8±332.6mg for women vs. 450.2±303.3mg for men; P<.001) and in the secondary causes of osteoporosis (13% of men vs. 6.5% of women; P<.001). In the sample, there were 404 fractures (20%), with a notable number of confirmed vertebral fractures (17.2%, 35.6% in men vs. 15.2% in women; P<.001) (AU)

Aceite de oliva y salud ósea / Olive oil and bone health

OBJETIVO: Existen en la literatura una serie de trabajos que demuestran que la incidencia de osteoporosis y fracturas asociadas es menor en países en los que la dieta mediterránea es predominante. El aceite de oliva es la principal característica común de toda la dieta mediterránea suponiendo un tercio de la ingesta de grasas vegetales. Se ha realizado una amplia revisión de trabajos que demuestran que la ingesta de aceite de oliva, tanto en animales de experimentación, en especial ratas ovariectomizadas, como en humanos, produce acciones positivas sobre el hueso. Se han revisado los efectos de diferentes componentes del aceite de oliva virgen como la oleuropeína, un compuesto fenólico, y otros alcoholes fenólicos como el tirosol y el hidrotirosol. La oleuropeína no sólo ejerce acciones sobre el hueso de ratas ovariectomizadas, sino que produce acciones sobre la formación de osteoblastos y desciende la formación de células "osteoclasto-like". Los compuestos fenólicos del aceite de oliva han demostrado ejercer acciones anti-oxidantes in vitro e in vivo. El tirosol y el hidrotirosol ejercen acciones sobre la pérdida de hueso en ratas ovariectomizadas e inhiben la formación de osteoclastos de modo dosis-dependiente. Un trabajo realizado por nuestro grupo ha demostrado que el aceite de oliva virgen ejerce también acciones sobre los parámetros biomecánicos del hueso como el módulo de Young y la dimensión fractal en ratas ovariectomizadas. Los resultados de esta revisión muestran que el aceite de oliva ejerce una acción positiva sobre la salud ósea. Sus componentes poseen propiedades anti-oxidantes y anti-inflamatorias, siendo candidatos potenciales para la prevención de la osteoporosis

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Profile of patients who visit medical internists for an osteoporosis assessment: The OSTEOMED registry. / Perfil de los pacientes que acuden al médico internista para valoración de osteoporosis: registro OSTEOMED.

BACKGROUND AND OBJECTIVES: Osteoporosis is considered a generalised skeletal disorder in which there is impaired bone resistance, which predisposes the individual to a greater risk of fracture. The aim of this cross-sectional study was to collect and present data on the main clinical characteristics of patients who consult medical internists in Spain. Understanding these characteristics can help in implementing action plans to improve these patients' care more effectively and efficiently. MATERIAL AND METHODS: Through an analysis of the Osteoporosis in Internal Medicine (OSTEOMED) registry, this study presents the main clinical characteristics of patients with osteoporosis who attended internal medicine consultations in 23 Spanish hospital centres between 2012 and 2017. We analysed the reasons for the consultations, the densitometric values, the presence of comorbidities, the prescribed treatment and other lifestyle-related factors. RESULTS: In total, 2024 patients with osteoporosis were assessed (89.87% women, 10.13% men). The patients' mean age was 64.1±12.1 years (women, 64.7±11.5 years; men, 61.2±14.2 years). There was no significant difference between the sexes in their history of recent falls (9.1% and 6.7%); however, there were significant differences in the daily intake of calcium from milk products (553.8±332.6mg for women vs. 450.2±303.3mg for men; P<.001) and in the secondary causes of osteoporosis (13% of men vs. 6.5% of women; P<.001). In the sample, there were 404 fractures (20%), with a notable number of confirmed vertebral fractures (17.2%, 35.6% in men vs. 15.2% in women; P<.001). A large portion of the patients did not undergo the indicated treatment and presented low levels of physical activity and sun exposure. A significant percentage of the patients presented associated comorbidities, the most common of which were hypertension (32%) and dyslipidaemia (28%). CONCLUSIONS: These results define the profile of patients with osteoporosis who attend internal medicine consultations in Spain. The results also show the multisystemic character of this condition, which, along with its high prevalence, determine that the specific internal medicine consultations dedicated to managing the condition are the appropriate place for caring for these patients.

Osteoporosis: concepto. Fisiopatología. Clínica. EpidemiologíaLa vitamina D en el siglo XXI. Más allá de la osteoporosis? / Osteoporosis: Concept. Pathophysiology.Clinical. Epidemiology

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Hemocromatosis y osteoporosis, a propósito de 4 casos / Hemochromatosis and osteoporosis, in reference to 4 cases

Aunque la mayoría de las enfermas con osteoporosis que observamos en la practica clínica obedecen al grupo de osteoporosis postmenopáusicas o las relacionadas con el envejecimiento, existen algunos casos de osteoporosis en cuyo desarrollo existe alguna enfermedad o factor identificable distinto a la menopausia o al envejecimiento; la mayoría de estas causas están relacionadas con la toma de esteroides, el hipogonadismo, los procesos malignos como el mieloma múltiple, la cirugía gástrica, el alcoholismo, y el tratamiento por anticonvulsivantes. La hemocromatosis hereditaria es otra situación relacionada con la aparición de osteoporosis. Presentamos 4 casos de pacientes con osteoporosis que padecen también hemocromatosis hereditaria, describiendo sus características y la posible relación de la hemocromatosis hereditaria con la patología ósea (AU)

Although most people's osteoporotic conditions treated in clinical practice may be categorized in the postmenopausal osteoporosis group or related to aging, there are some osteoporosis cases linked to the development of some other disease or identifiable factor. Most of these causes are associated with the taking of steroids, hypogonadism, malignant processes such as multiple myeloma, gastric surgery, alcoholism and treatment with anticonvulsant drugs. Hereditary hemochromatosis is another disorder related to the onset of osteoporosis. In this paper, we present 4 cases of patients with osteoporosis who also suffer hereditary hemochromatosis. The latter’s characteristics are described and also its possible relationship with bone disease (AU)

Acción de la vitamina K sobre la salud ósea / Action of vitamin K on bone health

Objetivos: Se admite hoy en día que la vitamina K tiene un papel importante en la salud ósea. Es necesaria para la gamma-carboxilación de la osteocalcina (la proteína no colágena más importante en el hueso), consiguiendo que la osteocalcina funcione. Hay dos formas importantes de la vitamina K (vitamina K1 y vitamina K2), que provienen de diferentes fuentes y tienen diferentes actividades biológicas. Estudios epidemiológicos sugieren que una dieta con niveles altos de vitamina K se asocia con un menor riesgo de fracturas de cadera en hombres ancianos y mujeres. Sin embargo, ensayos clínicos controlados y aleatorizados, realizados con suplementos de vitamina K1 o K2 en la población blanca, no muestran un aumento en la densidad mineral ósea (DMO) en la mayoría de las diferentes partes del esqueleto. Los suplementos con vitamina K1 y K2 pueden reducir el riesgo de fractura, pero los ensayos clínicos que incluyen las fracturas como resultado final tienen limitaciones metodológicas, por lo que se necesitarían ensayos clínicos con mayor número de pacientes y mejor diseñados para comprobar la eficacia de la vitamina K1 y K2 en las fracturas. Como conclusión, podríamos decir que actualmente no existe una evidencia suficiente para recomendar el uso rutinario de suplementos de vitamina K para la prevención de la osteoporosis y las fracturas en mujeres postmenopáusicas (AU)

Objetives: Nowadays it is recognised that vitamin K plays an important role in bone health. It is necessary for the gamma-carboxylation of osteocalcin (the most important non-collagen protein in the bone), making the osteocalcin function. There are two important forms of vitamin K (vitamin K1 and vitamin K2), which come from different sources and have different biological activity. Epidemiological studies suggest that a diet with high levels of vitamin K is associated with a lower risk of hip fractures in older men and in women. However, controlled randomised clinical trials, carried out with supplements of vitamin K1 or K2 in the white population do not show an increase in bone mineral density (BMD) in most of the different areas of the skeleton. Supplementation with vitamin K1 and K2 may reduce the risk of fracture, but the clinical trials which include fractures as a final result have methodological limitations, so clinical trials with greater numbers of patients, and which are better designed, would be needed in order to prove the efficacy of vitamin K1 and K2 in relation to fractures. In conclusion, we may say that there is currently insufficient evidence to recommend the routine use of vitamin K for the prevention of osteoporosis and fractures in postmenopausal women (AU)

Standardising the descriptive epidemiology of osteoporosis: recommendations from the Epidemiology and Quality of Life Working Group of IOF.

UNLABELLED: The Committee of Scientific Advisors of International Osteoporosis Foundation (IOF) recommends that papers describing the descriptive epidemiology of osteoporosis using bone mineral density (BMD) at the femoral neck include T-scores derived from an international reference standard. INTRODUCTION: The prevalence of osteoporosis as defined by the T-score is inconsistently reported in the literature which makes comparisons between studies problematic. METHODS: The Epidemiology and Quality of Life Working Group of IOF convened to make its recommendations and endorsement sought thereafter from the Committee of Scientific Advisors of IOF. RESULTS: The Committee of Scientific Advisors of IOF recommends that papers describing the descriptive epidemiology of osteoporosis using BMD at the femoral neck include T-scores derived from the National Health and Nutrition Examination Survey III reference database for femoral neck measurements in Caucasian women aged 20-29 years. CONCLUSIONS: It is expected that the use of the reference standard will help resolve difficulties in the comparison of results between studies and the comparative assessment of new technologies.

Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men.

CONTEXT: Strontium ranelate reduces vertebral and nonvertebral fracture risk in postmenopausal osteoporosis. OBJECTIVE: The objective of this study was to determine the efficacy and safety of strontium ranelate in osteoporosis in men over 2 years (main analysis after 1 year). DESIGN: This was an international, unbalanced (2:1), double-blind, randomized placebo-controlled trial (MALEO [MALE Osteoporosis]). SETTING: This international study included 54 centers in 14 countries. PARTICIPANTS: PARTICIPANTS were 261 white men with primary osteoporosis. INTERVENTION: Strontium ranelate at 2 g/d (n = 174) or placebo (n = 87) was administered. MAIN OUTCOME MEASURES: Lumbar spine (L2-L4), femoral neck, and total hip bone mineral density (BMD), biochemical bone markers, and safety were measured. RESULTS: Baseline characteristics were similar in both groups in the whole population (age, 72.9 ± 6.0 years; lumbar spine BMD T-score, -2.7 ± 1.0; femoral neck BMD T-score, -2.3 ± 0.7). Men who received strontium ranelate over 2 years had greater increases in lumbar spine BMD than those who received placebo (relative change from baseline to end, 9.7% ± 7.5% vs 2.0% ± 5.5%; between-group difference estimate (SE), 7.7% (0.9%); 95% confidence interval, 5.9%-9.5%; P < .001). There were also significant between-group differences in relative changes in femoral neck BMD (P < .001) and total hip BMD (P < .001). At the end of treatment, mean levels of serum cross-linked telopeptides of type I collagen, a marker of bone resorption, were increased in both the strontium ranelate group (10.7% ± 58.0%; P = .022) and the placebo group (34.9% ± 65.8%; P < .001). The corresponding mean changes of bone alkaline phosphatase, a marker of bone formation, were 6.4% ± 28.5% (P = .005) and 1.9% ± 25.4% (P = .505), respectively. After 2 years, the blood strontium level (129 ± 66 µmol/L) was similar to that in trials of postmenopausal osteoporosis. Strontium ranelate was generally well tolerated. CONCLUSIONS: The effects of strontium ranelate on BMD in osteoporotic men were similar to those in postmenopausal osteoporotic women, supporting its use in the treatment of osteoporosis in men.

Long-term treatment of osteoporosis in postmenopausal women: a review from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the International Osteoporosis Foundation (IOF).

INTRODUCTION: Postmenopausal osteoporosis is a chronic disease requiring treatment that balances long-term fracture efficacy against risk. METHODS: We reviewed the efficacy and safety of calcium and vitamin D, the selective estrogen receptor modulators (SERMs), the bisphosphonates, denosumab, and strontium ranelate in studies of 3 years or longer. RESULTS: Six trials lasted for 5 years, and seven went beyond that. The evidence beyond 5 years is generally weak, mainly due to methodological issues (open-label design, small samples, or absence of placebo control). Although calcium and vitamin D appear to be beneficial, the data are insufficient to evaluate benefits and risk beyond 3 years. The fracture efficacy of SERMs beyond 5 years is not known, though increases in bone mineral density (BMD) appear to be maintained. The SERMs have good long-term safety, including protective effects against breast cancer. The bisphosphonates have established fracture efficacy to 3 years, and 4 or 5 years with alendronate and risedronate. The evidence beyond 5 years indicates sustained increases in BMD. The safety of the bisphosphonates does not appear to be modified with time, with the possible exceptions of atypical subtrochanteric fracture and other events of unknown frequency. Denosumab has been tested up to 5 years, with continued increased in BMD and no reported safety issues. There is evidence for fracture efficacy of strontium ranelate, and sustained increases in BMD over 10 years. Strontium ranelate has good long-term safety. CONCLUSION: Robust long-term studies are relatively rare for the osteoporosis treatments, and generally show maintenance of BMD and, for some agents, an additional reduction in fracture incidence.

Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis.

UNLABELLED: In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. INTRODUCTION: Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. METHODS: Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX® scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX®-matched placebo group identified in the TROPOS placebo arm. RESULTS: The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 ± 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX®-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. CONCLUSIONS: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate.

Daily or monthly ibandronate prevents or restores deteriorations of bone mass, architecture, biomechanical properties and markers of bone turnover in androgen-deficient aged rats.

AIM: The aim of this study was to investigate the effects of the bisphosphonate ibandronate (IBN) in a male osteoporosis animal model. METHODS: Two studies were performed in 9-month-old orchidectomised (ORX) or sham-operated rats. In prevention study, subcutaneous IBN was administered daily (1 µg/kg) or monthly (28 µg/kg every 28 days) starting on day of surgery for 5 months. In treatment study, the same treatment started 6 months after ORX. After sacrifice, bone analyses by dual-energy X-ray absorptiometry, 3-dimensional micro-computed tomography, and 3-point bending were performed in femora or vertebrae. Serum tartrate-resistant acid phosphatase 5b (TRAP-5b) and aminoterminal propeptide of collagen I (PINP) were analysed for resorption and osteocalcin (BGP) for bone formation. RESULTS: In both studies, ORX resulted in significant femoral and vertebral bone loss and microarchitectural deterioration after 5 months of ORX, and became more pronounced after 11 months. Biomechanical strength was also decreased. Serum levels for TRAP-5b and BGP increased while PINP levels were reduced or unchanged. Both daily and monthly IBN prevented or even restored ORX-induced changes in both studies, with the intermittent regimen showing a improvement in efficacy with respect to many of the biomechanical parameters.

The effectiveness of intermittent rat parathyroid hormone (1-34) treatment on low bone mass due to oestrogen or androgen depletion in skeletally mature rats.

Rat parathyroid hormone (PTH) 1-34 (4 microg/kg/day) was applied for 2.5 months to 9 month-old rats immediately after ovariectomy or orchidectomy or to 15 month-old rats with low bone mass which had been castrated 6 months before in order to know the effects on serum biochemistry parameters, lumbar and femoral bone mineral density, histology, cancellous and cortical bone histomorphometry, mineralisation content profile in cortical bone by backscattered-electron microscopy, and femoral torsion biomechanical testing. In ovariectomised rats, preventive PTH treatment avoided cancellous bone loss in tibial metaphysis and partially in lumbar vertebra, while in cortical bone, PTH increased endosteal resorption and periosteal formation. In intervention study, PTH did not restore cancellous bone but a strong endosteal and periosteal new bone formation was detected. In orchidectomised rats, PTH, in preventive study, avoided cancellous bone loss in metaphysis and lumbar vertebra, and a mild new bone formation in cortical bone was found. In intervention study, PTH maintained baseline cancellous bone mass, but in cortical bone a strong endosteal and periosteal new bone formation was detected. The PTH-induced new bone formation was confirmed by histology and by mineral content profiles. After castration, biomechanical properties were affected in females but not in male rats and PTH reverted this effect.

Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover.

UNLABELLED: Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels. INTRODUCTION: Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels. METHODS: Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo. RESULTS: In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290). CONCLUSION: The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states.

Bone disease induced by phenytoin therapy: clinical and experimental study.

Previous studies have made references to prolonged treatment with phenytoin as a possible risk factor in the development of osteoporosis and/or osteomalacia. We studied a group of 30 epileptic patients who were under long-term treatment with phenytoin (DPH) in an ambulatory regimen. We found the prevalence of osteoporosis to be 3.3% and of osteopenia to be 56.6%, affecting predominantly the femur, without any significant decrease in bone mineral density of the lumbar spine. These patients were showing signs of bone turnover uncoupling with increases in bone resorption markers. At this time, they also exhibited slight alterations in their phosphocalcium metabolism with trends to hypocalcemia and secondary hyperparathyroidism that was found not to be caused by a vitamin D deficiency as the serum levels of 25(OH)D and 1,25(OH)(2)D were normal. With the aims of corroborating these results and to investigate the physiopathological effects on the bone induced by anticonvulsant drugs we developed a further experimental study in which we administered DPH over a 6-week period with a dose of 5 g/kg/day to male Wistar rats that were in the growth phase. This treatment produced a decrease in overall BMD and bone mineral content in the femur. We did not find osteomalacia in the vertebral biopsy, but the administration of DPH to these animals decreased trabecular volume as well as lessened the thickness of osteoid edges together with an uncoupling in bone turnover. There was also a marked decrease in bone formation and a tendency towards increased bone resorption. We have also found a decrease in resistance to fracture by torsion in the biomechanical assay, which translates into an increase in bone fragility. In these male Wistar rats, the administration of DPH produced a tendency towards increasing the markers of resorption and, though changes in serum levels of calcium and phosphorus were not observed, to provoke an increase in the parathyroid hormone levels; with normal levels of 1,25(OH)(2)D which has produced the same inclination in rats as in humans.

Osteoporosis masculina / No disponible

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Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis.

SUMMARY: Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. INTRODUCTION: Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. METHODS: A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. RESULTS: Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST(R), was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. CONCLUSION: In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.

Effect of risedronate on bone mass, remodelling and biomechanical strength in orchidectomized rats.

BACKGROUND: The ability of risedronate to prevent and/or treat orchidectomy-induced osteoporosis in male rats was studied. METHODS: Ninety-five 10-week-old male Wistar rats were sham-operated or orchidectomized. Prevention study: Sham: sham-operated rats; ORX: orchidectomized rats; ORX + RSD: orchidectomized rats, treated for 6 weeks with risedronate. Animals were sacrificed 6 weeks after surgery. Treatment study: Sham(1) and ORX(1): sham and orchidectomized rats sacrificed 3 months after orchidectomy; Sham(2), ORX(2) and ORX(2) + RSD: sham-operated, and orchidectomized rats treated with placebo or risedronate for 6 weeks starting 3 months after orchidectomy, and then sacrificed. Risedronate (0.5 mg/kg/day) and placebo (saline) were administered via oral gavage. After sacrifice, bone mineral density by DEXA, bone volume (BV/TV), osteocalcin (BGP), and serum carboxyterminal telopeptide of collagen type I (CTX) were measured. Femur low-rate torsion testing was performed. RESULTS: Orchidectomy produced an increase in bone remodelling with loss of BV/TV, without effects on torsional strength. Risedronate treatment partially prevented these effects. In the treatment study, risedronate reduced bone remodelling and restored BV/TV to levels higher than those of the sham group, improving biomechanical parameters. CONCLUSIONS: These results suggest that risedronate could be used as a prevention or treatment of male osteoporosis due to hypogonadism.