Treatment of Paget\u27s Bone Disease with the Bisphosphonate APD

Thirty-two patients with Paget\u27s bone disease have been treated with the bisphosphonate APD. Nineteen had previously received treatment for Paget\u27s disease with EHDP alone or in combination with calcitonin; 13 had not previously received treatment for Paget\u27s disease. APD was given in a mean dose of 6.8 mg/kg of body weight during a period of 6 to 12 months. Bone pain disappeared or diminished in 91% of the patients. A very significant diminution of the biochemical indices of bone turnover was observed in all patients, but the response occurred faster in patients who had not previously received treatment for Paget\u27s disease. In 10 patients, APD therapy was discontinued after biochemical remission of the Paget\u27s disease had been achieved. In most patients, clear signs of reactivation of the disease appeared 9 to 10 months after APD therapy was discontinued

Sarcopenia: clinical approach

La sarcopenia, disminución de la masa y rendimiento muscular, es un importante factor de riesgo para la salud en general e, independientemente de la densidad mineral, aumenta el riesgo de sufrir fracturas no vertebrales, especialmente en el hombre. La masa muscular alcanza su mayor desarrollo alrededor de los 40 años y luego disminuye constantemente. Aun después de los 70 años puede disminuir anualmente alrededor del 1% en el hombre y 0,5% en la mujer. Desde el punto de vista clínico, la mejor valoración es la medición de la masa muscular apendicular por DXA. El estudio debe incluir prueba de fuerza (apriete del puño), potencia (pararse/sentarse, subir escalones) y rendimiento (velocidad de la marcha) muscular. La detección/diagnóstico de la sarcopenia debería efectuarse en los sujetos mayores de 65 años e incluso en los menores de esa edad, si sufren caídas frecuentes, fracturas osteoporóticas o falta de fuerza manifiesta. Las intervenciones destinadas a restaurar o prevenir la pérdida de masa y rendimiento muscular deben incluir ejercicios de resistencia, dieta con contenido proteico de 1,0 a 1,2 g/kg de peso y administración de vitamina D para mantener niveles de 25 HOD mayores de 30 ng/ml. Los agentes terapéuticos en investigación incluyen, entre otros, a los anticuerpos antimiostatina y los SARM (moduladores selectivos de los andrógenos).Sarcopenia, the diminution of muscular mass and performance, is an important risk factor for general health and specifically for bone fractures independently of the bone mineral density. After reaching a maximal development around 40 years of age, the muscular mass (MM) diminishes constantly, even after 70 years of age at a rate of 1% per year in men and 0.5% per year in women. From the clinical approach the best measure of MM is accomplished by DXA measuring the appendicular MM. The study of the patient should include physical test to assess strength (hand grip), power (sit/stand test and climb stairs) and muscular performance (walking speed). Subjects over 65 years of age, or those with frequent fall, osteoporotic fractures or manifest diminution of their physical performance could undergo studies for sarcopenia detection. Medical interventions to restore or prevent MM loss should include resistance exercises, protein content of the diet between 1.0 to 1.2 g/kg and vitamin D administration to keep 25 HOD over 30 ng/ml. Intensive research of new agents include, among others, antibodies anti-miostatin and SARM.Fil: Mastaglia, Silvina Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Mautalen, Carlos Alfredo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Acute Effect of Piretanide upon Serum and Urinary Calcium in Normal Subjects

We gave piretanide, a new diuretic, at two dose levels to six normal subjects. Sodium excretion increased six to eightfold in the first two hours, and diuresis was completed within four hours. There was a simultaneous increase in the excretion of calcium which exceeded the amount present In the mobilized extracellular fluid. The resulting deficit of calcium produced a small but significant fall in serum calcium corrected for protein. After diuresis ended, calcium was retained but not sodium, when compared to basal values on the previous day. The fall in urinary calcium and the failure to correct the sodium deficit may both have resulted from increased secretion of parathyroid hormone (PTH), which increases calcium reabsorption and decreases sodium reabsorption. The role of PTH in the long-term effects of diuretics on sodium and calcium excretion requires further study

Peripheral bone mass is not affected by winter vitamin D deficiency in children and young adults from Ushuaia

Low vitamin D levels in elderly people are associated with reduced bone mass, secondary hyperparathyroidism, and increased fracture risk. Its effect on the growing skeleton is not well known. The aim of this study was to evaluate the possible influence of chronic winter vitamin D deficiency and higher winter parathyroid hormone (PTH) levels on bone mass in prepubertal children and young adults. The study was carried out in male and female Caucasian subjects. A total of 163 prepubertal children (X age ± 1 SD: 8.9 ± 0.7 years) and 234 young adults (22.9 ± 3.6 years) who had never received vitamin D supplementation were recruited from two areas in Argentina: (1)Ushuaia (55°South latitude), where the population is known to have low winter 25OHD levels and higher levels of PTH in winter than in summer, and (2)Buenos Aires (34°S), where ultraviolet (UV) radiation and vitamin D nutritional status in the population are adequate all year round. Bone mineral content (BMC) and bone mineral density (BMD) of the ultradistal and distal radius were measured in the young adults. Only distal radius measurements were taken in the children. Similar results were obtained in age-sex matched groups from both areas. The only results showing significant difference corresponded to comparison among the Ushuaian women: those whose calcium (Ca) intake was below 800 mg/day presented lower BMD and BMC values than those whose Ca intake was above that level (0.469 ± 0.046 versus 0.498 ± 0.041 g/cm2, P < 0.02; 3.131 ± 0.367 versus 3.339 ± 0.386 g, P < 0.05, respectively). In conclusion, peripheral BMD and BMC were similar in children and young adults from Ushuaia and Buenos Aires in spite of the previously documented difference between both areas regarding UV radiation and winter vitamin D status. BMD of axial skeletal areas as well the concomitant effect of a low Ca diet and vitamin D deficiency on the growing skeleton should be studied further.Fil: Oliveri, María Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Wittich, A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Mautalen, Carlos Alfredo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chaperon, Federico. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Kizlansky, A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; Argentin

High Prevalence of Sarcopenia in Women with Osteoporotic Fractures

The aim of the present study was to assess the prevalence of sarcopenia in women with osteopenia/osteoporosiswith or without fragility fractures.Patients and methods: 112 ambulatory women with osteopenia/osteporosis were included. Body composition wasdetermined by DXA. Weight, height, body mass index (BMI), bone mineral density (BMD) of the total skeleton, totallean mass (LM), appendicular lean mass (ALM) and the index: appendicular lean mass/height² (ALM/h²) weredetermined. Grip strength and self-selected gait speed were assessed. Results: Average (X ± SD) results were: age70.9 ± 8.2 years, BMI: 23.1 ± 3.3 kg/h², total skeleton BMD T-Score:-1.7 ± 0.8, total LM 33.3 ± 3.8 kg, ALM 14.4 ±2.1kg and ALM/h²: 5.86 ± 0.68 kg/h². Walking speed 0.96±0.21m/s and handgrip: 18.8 ± 4.8 kg. The prevalence ofsarcopenia was: 24.7% (International Working Group criteria). Values for BMI, LM, ALM, ALM/h², gait speed andhand grip were significantly lower in sarcopenic vs. non-sarcopenic patients. 29 patients, average age: 70.5 ± 8.0years had osteoporotic fragility fractures (Fx). The prevalence of sarcopenia in the group of patients with Fx was41.4% vs. 19.3% in the non-Fx patients (n=83) (p<0.018).Conclusion: The prevalence of sarcopenia in women with osteopenia/osteoporosis was higher compared to thatusually reported in non-selected patients of similar age. Those with bone fractures had a significantly higherprevalence of sarcopenia compared to the non-fracture patients. The assessment of muscle mass and function inpatients with osteopenia/osteoporosis is recommended.Fil: Fernández, Candela. Centro de Osteopatías Médicas Dr Mautalen; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Bagur, Alicia Cristina. Centro de Osteopatías Médicas Dr Mautalen; ArgentinaFil: Gomez Glorioso, Dolores. Centro de Osteopatías Médicas Dr Mautalen; ArgentinaFil: González, Diana. Centro de Osteopatías Médicas Dr Mautalen; ArgentinaFil: Mastaglia, Silvina Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Mautalen, Carlos Alfredo. Centro de Osteopatías Médicas Dr Mautalen; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study

The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile. INTRODUCTION: This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis. METHODS: Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively. RESULTS: Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed. CONCLUSIONS: Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile

Prediction of Incident Hip Fracture with the Estimated Femoral Strength by Finite Element Analysis of DXA Scans in the Study of Osteoporotic Fractures

A bone fractures only when loaded beyond its strength. The purpose of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of DXA scans, with incident hip fracture in comparison to hip BMD, FRAX(®) and hip structure analysis (HSA) variables. This prospective case-cohort study included a random sample of 1941 women and 668 incident hip fracture cases (295 in the random sample) during a mean±SD follow-up of 12.8±5.7 yrs from the Study of Osteoporotic Fractures (n=7860 community-dwelling women ≥67 yr of age). We analyzed the baseline DXA scans (Holgoic 1000) of the hip using a validated plane-stress, linear-elastic finite element (FE) model of the proximal femur and estimated the femoral strength during a simulated sideways fall. Cox regression accounting for the case-cohort design assessed the association of estimated femoral strength with hip fracture. The age-BMI-adjusted hazard ratio (HR) per SD decrease for estimated strength (2.21, 95% CI 1.95–2.50) was greater than that for TH BMD (1.86, 95% CI 1.67–2.08; p<0.05), FN BMD (2.04, 95% CI 1.79–2.32; p>0.05), FRAX(®) scores (range 1.32–1.68; p<0.0005) and many HSA variables (range 1.13–2.43; p<0.005), and the association was still significant (p<0.05) after further adjustment for hip BMD or FRAX(®) scores. The association of estimated strength with incident hip fracture was strong (Harrell's C index 0.770), significantly better than TH BMD (0.759, p<0.05) and FRAX(®) scores (0.711–0.743, p<0.0001) but not FN BMD (0.762, p>0.05) Similar findings were obtained for intra- and extra-capsular fractures. In conclusion, the estimated femoral strength from FE analysis of DXA scans is an independent predictor and performs at least as well as FN BMD in predicting incident hip fracture in postmenopausal women

Cortical bone assessed with clinical computed tomography at the proximal femur.

Hip fractures are the most serious of all fragility fractures in older people of both sexes. Trips, stumbles, and falls result in fractures of the femoral neck or trochanter, and the incidence of these two common fractures is increasing worldwide as populations age. Although clinical risk factors and chance are important in causation, the ability of a femur to resist fracture also depends on the size and spatial distribution of the bone, its intrinsic material properties, and the loads applied. Over the past two decades, clinical quantitative computed tomography (QCT) studies of living volunteers have provided insight into how the femur changes with advancing age to leave older men and women at increased risk of hip fractures. In this review, we focus on patterns of cortical bone loss associated with hip fracture, age-related changes in cortical bone, and the effects of drugs used to treat osteoporosis. There are several methodologies available to measure cortical bone in vivo using QCT. Most techniques quantify bone density (g/cm(3)), mass (g), and thickness (mm) in selected, predefined or “traditional” regions of interest such as the “femoral neck” or “total hip” region. A recent alternative approach termed “computational anatomy,” uses parametric methods to identify systematic differences, before displaying statistically significant regions as color-scaled maps of density, mass, or thickness on or within a representative femur model. This review will highlight discoveries made using both traditional and computational anatomy methods, focusing on cortical bone of the proximal femur.This work was supported by Cambridge NIHR Biomedical Research Centre (Metabolism, Endocrinology, Bone and Biomaterials Theme), Arthritis Research UK (a Research Progression award to KESP). TDT is a Wellcome Trust Clinical Research Fellow. The femurs shown in Fig. 2 are courtesy of the Melbourne Femur Collection, Chairman Professor John Clement (Melbourne Dental School).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.219

Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density.

Funder: NIHR Cambridge BRC; Id: http://dx.doi.org/10.13039/501100018956Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).This research was funded by Amgen and supported by the NIHR Cambridge BRC. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care