Three-year effect of bisphosphonates on bone mineral density after denosumab withdrawal: observations from a real-world study.

Data on long-term treatment regimens for preventing bone mineral density (BMD) loss that occurs after denosumab (Dmab) withdrawal are scarce. Our aim was to evaluate the long-term changes (12-36 months) in BMD and bone turnover markers in a group of postmenopausal women who had been treated with Dmab and received subsequent treatment with bisphosphonates. Secondary objectives were to evaluate factors associated with BMD loss, to compare the BMD change in patients who received oral vs intravenous bisphosphonates, and to assess the frequency of fragility fractures after Dmab discontinuation. The clinical data of 54 patients, 26 of whom had clinical and DXA assessments at 36 months, were analyzed. After 12 months, the mean LS BMD had decreased by 2.8% (±5.0), FN BMD by 1.9% (±5.8), and TH BMD by 1.9% (±3.7). After 36 months, LS BMD had decreased by 3.7% (±6.7), FN BMD by 2.5% (±7.1), and TH BMD by 3.6% (±5.2). C-terminal cross-linked telopeptide of type I collagen significantly increased during the first 12 months after Dmab withdrawal but then decreased at 36 months. BMD loss at 12 months was higher in patients with more than 30 months of Dmab treatment, but this difference was only statistically significant at FN (-3.3% vs -0.3%, P = .252 at LS, -3.3% vs 0.3%, P = .033 at FN, and -2.1% vs 0.9, P = .091 at TH). There were no statistically significant differences regarding the change in BMD at 12 and 36 months between oral and intravenous treatment. Seven patients suffered incidental vertebral fractures (clinical vertebral fractures: n = 6, morphometric fractures: n = 1) three of which were multiple. None of these patients were treated following international or institutional guidelines or recommendations. In summary, our study suggests that bisphosphonates can help maintain BMD for 36 months after Dmab discontinuation.

Twenty-four months of follow-up in women with rebound-associated vertebral fractures after discontinuation of denosumab: a single-centre case series.

Evidence on the management of rebound-associated vertebral fractures after denosumab discontinuation is scarce. This study describes seven patients retreated with denosumab, teriparatide or zoledronate for 24 months. Their bone mineral density remained stable or improved and no new fractures occurred suggesting that all three options might be adequate for their treatment. PURPOSE: To describe the densitometric and biochemical changes achieved with osteoactive treatment after 24 months of follow-up in patients who suffered rebound-associated vertebral fractures (RAVFs) after Dmab discontinuation, and to report the occurrence of new vertebral and non-vertebral fractures. METHODS: Patients with RAVFs who received retreatment (RT) for 24 months were included. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH), along with C-terminal cross-linked telopeptide of type I collagen, osteocalcin, and bone alkaline phosphatase. Data were collected at the start of the RT and after 24 months. RESULTS: Seven female patients were included. RT consisted in Dmab (n = 3), teriparatide (TPT) (n = 3) and zoledronate (Zol) (n = 1). At 24 months, the mean BMD change was 2.2% at LS, 6.8% at FN and 3.8% at TH in the Dmab group, 7.5% at LS, 1.4% at FN and 3.7% at TH in the TPT group and, 5.0% at LS, 0.6% at FN and 3.9% at TH in the patient with Zol. After 24 months of follow-up, no patient suffered new fractures. CONCLUSION: In this series of patients with RAVFs, we did not observe any new fractures and the BMD remained stable after 24 months of RT. Future studies are needed to evaluate the most suitable treatment approach after RAVFs but these preliminary data suggest that all denosumab, zoledronate and teriparatide might be adequate options.

Recent Insights into Pregnancy and Lactation-Associated Osteoporosis (PLO).

During pregnancy and lactation, female physiology adapts to fulfill the fetal and neonatal calcium and phosphorus requirements. The physiological changes that take place during these periods do not affect maternal skeleton resistance to fracture in most of the cases. However, there is a small percentage of women that do experience fragility fractures during these times of life. Pregnancy and lactation-associated osteoporosis (PLO) is an infrequent condition defined by the occurrence of non-traumatic fractures - most frequently vertebral - during the third trimester of gestation and/or the first months of postpartum. Its physiopathology has not yet been completely elucidated. Several authors have reported that risk factors for secondary osteoporosis might be present in up to 80% of the cases of PLO patients. According to recent studies, genetic factors might also play a relevant role in PLO. Given its rarity, the available literature on this condition is limited. Most of the published data consist on case reports and case series articles. There are not any randomized controlled trials regarding this disorder. Although there is consensus about discontinuation of lactation and calcium and vitamin D supplementation as the first steps in the treatment of these patients, there is still controversy regarding the long-term and/or pharmacological management of this condition. Recent data on the use of teriparatide in this population looks promising. In this review, we aimed to revise and summarize current knowledge about the physiopathology and management of PLO.

Descriptive assessment of 54 cases with complex regional pain syndrome in lower limbs / Evaluación descriptiva de 54 casos con síndrome dolo roso regional complejo en miembros inferiores

Abstract Introduction: Complex regional pain syndrome (CRPS), also known as Sudeck syndrome, is a chronic painful condition usually affecting the limbs after trauma or surgery. Its presentation is heterogeneous and its physio pathology, diagnosis and treatment remain controversial. The objective of this study was to analyze a group of patients with this rare syndrome, describing in detail the results of the dual energy X-ray absorptiometry (DXA) and the response to bisphosphonate treatment. Method: We retrospectively analyzed 54 patients with CRPS, taking into account their demographic features, inciting events and diagnostic tests. As regards treat ment, we analyzed the results and adverse events of the use of bisphosphonates Results: We found a female predominance (74%), with 55 ± 13 years. The most common inciting event was trauma (59%), followed by surgery. The difference in bone mineral density between the affected limb and the healthy one was 12 to 15%. Forty-four patients were treated with bisphosphonates (pamidronate, iban dronate, zoledronic acid) and showed a clinical im provement, mainly in terms of pain intensity. Only six patients presented with adverse events, like pseudoflu syndrome and acute phase symptoms. Conclusion: In our cohort, lower limbs CRPS pre dominantly affects middle aged women. DXA scans are tests used to quantify bone loss and the response to treatment. The use of bisphosphonates is an interest ing therapeutic option to improve clinical symptoms in most patients. Future prospective randomized studies will be needed to confirm our results.

Resumen Introducción: El síndrome doloroso regional complejo (SDRC), también conocido como síndrome de Sudeck, es una enfermedad dolorosa crónica que generalmente afecta a las extremidades luego de un trauma o cirugía. Su presentación es heterogénea y existen controversias sobre su fisiopatología, adecuado diagnóstico y trata miento. El objetivo de este trabajo es describir un grupo de pacientes con SDRC en miembros inferiores, describi endo los resultados de la densitometría mineral ósea (DMO) y la respuesta al tratamiento con bifosfonatos. Método: Analizamos retrospectivamente 54 pacientes con SDRC, teniendo en cuenta características demográ ficas, factores desencadenantes y estudios diagnósticos. En relación al tratamiento, analizamos los resultados y efectos adversos del uso de bifosfonatos. Resultados: Encontramos un predominio femenino (74%), con una edad de 55 ± 13 años. Los factores des encadenantes más comunes fueron los traumatismos (59%) y la cirugía. La diferencia de densidad mineral ósea entre el miembro comprometido y el sano fue 12 a 15%. En los 44 pacientes fueron tratados con bifosfona tos (pamidronato, ibandronato y ácido zoledrónico), su uso se asoció a mejoría clínica, especialmente del dolor. Seis pacientes tuvieron efectos adversos como sindrome pseudogripal y síntomas de fase aguda. Conclusión: En nuestra población, el SDRC de miem bros inferiores predomina en mujeres de edad media. La DMO es un método que permite cuantificar la pérdida ósea y la respuesta al tratamiento. Los bifosfonatos son una buena opción terapéutica para el control de síntomas. Son necesarios futuros estudios de naturaleza prospectiva y aleatorizada para confirmar nuestros resultados.

Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

OBJECTIVE: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years. METHODS: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%. RESULTS: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios. CONCLUSIONS: This GIO guideline provides evidence-based guidance for health care providers treating patients.

Descriptive assessment of 54 cases with complex regional pain syndrome in lower limbs.

INTRODUCTION: Complex regional pain syndrome (CRPS), also known as Sudeck syndrome, is a chronic painful condition usually affecting the limbs after trauma or surgery. Its presentation is heterogeneous and its physiopathology, diagnosis and treatment remain controversial. The objective of this study was to analyze a group of patients with this rare syndrome, describing in detail the results of the dual energy X-ray absorptiometry (DXA) and the response to bisphosphonate treatment. METHOD: We retrospectively analyzed 54 patients with CRPS, taking into account their demographic features, inciting events and diagnostic tests. As regards treatment, we analyzed the results and adverse events of the use of bisphosphonates Results: We found a female predominance (74%), with 55 ± 13 years. The most common inciting event was trauma (59%), followed by surgery. The difference in bone mineral density between the affected limb and the healthy one was 12 to 15%. Forty-four patients were treated with bisphosphonates (pamidronate, ibandronate, zoledronic acid) and showed a clinical improvement, mainly in terms of pain intensity. Only six patients presented with adverse events, like pseudoflu syndrome and acute phase symptoms. CONCLUSION: In our cohort, lower limbs CRPS predominantly affects middle aged women. DXA scans are tests used to quantify bone loss and the response to treatment. The use of bisphosphonates is an interesting therapeutic option to improve clinical symptoms in most patients. Future prospective randomized studies will be needed to confirm our results.

Introducción: El síndrome doloroso regional complejo (SDRC), también conocido como síndrome de Sudeck, es una enfermedad dolorosa crónica que generalmente afecta a las extremidades luego de un trauma o cirugía. Su presentación es heterogénea y existen controversias sobre su fisiopatología, adecuado diagnóstico y tratamiento. El objetivo de este trabajo es describir un grupo de pacientes con SDRC en miembros inferiores, describiendo los resultados de la densitometría mineral ósea (DMO) y la respuesta al tratamiento con bifosfonatos. Método: Analizamos retrospectivamente 54 pacientes con SDRC, teniendo en cuenta características demográficas, factores desencadenantes y estudios diagnósticos. En relación al tratamiento, analizamos los resultados y efectos adversos del uso de bifosfonatos. Resultados: Encontramos un predominio femenino (74%), con una edad de 55 ± 13 años. Los factores desencadenantes más comunes fueron los traumatismos (59%) y la cirugía. La diferencia de densidad mineral ósea entre el miembro comprometido y el sano fue 12 a 15%. En los 44 pacientes fueron tratados con bifosfonatos (pamidronato, ibandronato y ácido zoledrónico), su uso se asoció a mejoría clínica, especialmente del dolor. Seis pacientes tuvieron efectos adversos como sindrome pseudogripal y síntomas de fase aguda. Conclusión: En nuestra población, el SDRC de miembros inferiores predomina en mujeres de edad media. La DMO es un método que permite cuantificar la pérdida ósea y la respuesta al tratamiento. Los bifosfonatos son una buena opción terapéutica para el control de síntomas. Son necesarios futuros estudios de naturaleza prospectiva y aleatorizada para confirmar nuestros resultados.

Effect of Teriparatide on Bone Mineral Density and Bone Markers in Real-Life: Argentine Experience.

Purpose: To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone markers under clinical practice conditions. To assess whether the results in real-life match those published in clinical trials. Methods: Cross-sectional study of postmenopausal women treated with TPTD for at least 12 months. Results: 264 patients were included in the study. Main characteristics are as follows: age: 68.7 ± 10.2 years, previous fractures: 57.6%, and previously treated with antiresorptive (AR-prior): 79%. All bone turnover markers studied significantly increased after 6 months. CTX and BGP remained high up to 24 months, but total and bone alkaline phosphatase returned to basal values at month 18. There was a significant increase in lumbar spine (LS) BMD after 6 months (+6.2%), with a maximum peak at 24 months (+13%). Femoral neck (FN) and total hip (TH) BMD showed a significant increase later than LS (just at month 12), reaching a maximum peak at month 24 (FN + 7.9% and TH + 5.5%). A significant increase in LS BMD was found from month 6 to month 24 compared to basal in both AR-naïve, and AR-prior patients (+16.7% and +10.5%, respectively), without significant differences between the two groups. Comparable results were found in FN and TH BMD. Main conclusions. As reported in real-life clinical studies, treatment of osteoporotic postmenopausal women with TPTD induced a significant increase in bone turnover markers from month 6 onward and an increase in BMD from months 6-12 with continuous gain up to month 24. The real-life results of our study matched the results of randomized clinical trials. In addition, TPTD induced an increase in BMD, regardless of the previous use of AR.

Alliance for the development of the Argentinian Hip Fracture Registry.

Age expectancy has significantly increased over the last 50 years, as well as some age-related health conditions such as hip fractures. The development of hip fracture registries has shown enhanced patient outcomes through quality improvement strategies. The development of the Argentinian Hip Fracture Registry is going in the same direction. INTRODUCTION: Age expectancy has increased worldwide in the last 50 years, with the population over 64 growing from 4.9 to 9.1%. As fractures are an important problem in this age group, specific approaches such as hip fracture registries (HFR) are needed. Our aim is to communicate the Argentinian HFR (AHFR) development resulting from an alliance between Fundación Trauma, Fundación Navarro Viola, and the Argentinian Network of Hip Fracture in the elderly. METHODS: Between October 2020 and May 2021, an iterative consensus process involving 5 specialty-focused meetings and 8 general meetings with more than 20 specialists was conducted. This process comprised inclusion criteria definitions, dataset proposals, website deployment with data protection and user validation, the definition of hospital-adjusted registry levels, implementation planning, and sustainability strategies. RESULTS: By June 2021, we were able to (1) outline data fields, including epidemiological, clinical, and functional dimensions for the pre-admission, hospitalization, discharge, and follow-up stages; (2) define three levels: basic (53 fields), intermediate (85), and advanced (99); (3) identify 21 benchmarking indicators; and (4) make a correlation scheme among fracture classifications. Simultaneously, we launched a fundraising campaign to implement the AHFR in 30 centers, having completed 18. CONCLUSION: AHFR development was based on four pillars: (1) representativeness and support, (2) solid definitions from onset, (3) committed teams, and (4) stable funding. This tool may contribute to the design of evidence-based health policies to improve patient outcomes, and we hope this experience will help other LMICs to develop their own tailored-to-their-needs registries.

Exploring the Differences Between Dominant and Nondominant Feet and Hands Bone Mineral Density.

The assessment of regional bone mineral density (BMD) has proved to be useful for illustrating the impact of focal bone demineralization diseases on bone mass. In these scenario, a common practice is to compare the affected limb with the contralateral limb. However, there are no studies comparing BMD differences between dominant vs nondominant limbs at these sites. In addition, most studies have assessed BMD in specific ROIs (regions of interests) instead of in the whole limb. The purpose of our study was to compare the BMD of dominant vs nondominant hands and feet in healthy individuals, using both the whole limb software and specific ROIs. We performed a cross-sectional analysis on untrained women and men over 18 years of age who volunteered to participate. BMD (g/cm2), bone area (cm2) and BMC (bone mineral content) (g) were measured by Lunar Prodigy DXA (GE Healthcare, Madison, WI, USA), using 2 different approaches: whole limb/region software and specific ROIs. A total of 42 subjects (11 men and 31 women) were included. Mean age was 44.19 ± 10.49 years. BMD was greater in the dominant in comparison with the nondominant hand. The difference was 0.014 (95% CI, 0.009-0.018) for the whole hand BMD, 0.023 (95% CI, 0.003-0.044) for ROI 1, and 0.016 (95% CI, 0.003-0.029) for ROI 2. No significant differences were found between dominant and nondominant foot BMD, using the whole limb software and specific ROIs. To our knowledge, this is the first study to explore the differences in BMD, bone area and BMC in terms of limb dominance, supporting the usefulness of DXA as an accurate and objective complementary diagnostic or follow-up tool in focal bone demineralization diseases.

Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.

Which is the best antiresorptive treatment after finishing teriparatide?

Anabolic drugs are the treatment of choice for osteoporotic patients with very high risk of fractures. Post anabolic treatment with an antiresorptive drug maintains the bone mineral density (BMD) gained. The recommendations regarding the ideal antiresorptive drug are not precise. The aim of this paper is to compare the usefulness of zoledronate and denosumab in a group of 28 women with very high risk of fractures. All of them completed at least one year of treatment with teripatide and latter 14 received zolendronate and 14 denosumab for another year. We retrospectively review their biochemical and densitometric changes. Both treatment groups experienced a reduction in bone turnover markers of the same magnitude at the end of the second year. In Lumbar Spine BMD increase of 3.96 ± 8.56% Median (Me) 2.54 p = 0.21 in zolendronate group and 3.55 ± 5.36% (Me 5.14) p = 0.07 in denosumab group. Femoral Neck BMD changed -0.09 ± 6.50% (Me 0.29) p = 0.85 in zolendronate group, and - 3.41 ± 5.08% (Me 5.35) p = 0.59 in denosumab group, with no difference between both groups. In Total Hip BMD an increase of 0.55 ± 4.20% (Me 0.43) p = 0.70 in zoledronate group, and 4.53 ± 5.13% (Me 0.64) p = 0.04 with denosumab. We conclude that both antiresortive treatments have a similar effect in biochemical markers after one year of treatment. BMD increase significantly in total hip and changed with a trend toward in lumbar spine with denosumab, but without differences between both groups of treatment.

Los anabólicos son el tratamiento de elección en la osteoporosis con muy alto riesgo de fracturas. Después del tratamiento anabólico un fármaco antirresortivo mantiene la densidad mineral ósea (DMO) ganada. Las recomendaciones sobre el fármaco antirresortivo ideal no son precisas. El objetivo de este trabajo es comparar la utilidad de zoledronato y denosumab en un grupo de 28 mujeres con muy alto riesgo de fracturas. Todas ellas completaron al menos un año de tratamiento con teripatide y luego 14 recibieron zolendronato y 14 denosumab durante un año. Revisamos retrospectivamente sus cambios bioquímicos y densitométricos. Ambos grupos de tratamiento experimentaron una reducción de los marcadores de recambio óseo de la misma magnitud al final del segundo año. En columna lumbar la DMO aumentó 3.96 ± 8.56% Mediana (Me) 2.54, p = 0.21 en el grupo zolendronato y 3.55 ± 5.36% (Me 5.14) p = 0.07 en el grupo denosumab. La DMO del cuello femoral cambió -0.09 ± 6.50% (Me 0.29) p = 0.85 en el grupo zolendronato y - 3.41 ± 5.08% (Me 5.35) p = 0.59 en el grupo de denosumab, sin diferencias entre ambos grupos. En la Cadera Total la DMO aumentó 0.55 ± 4.20% (Me 0.43) p = 0.70 con zoledronato y 4.53 ± 5.13% (Me 0.64) p = 0.04 con denosumab. Concluimos que ambos tratamientos antiresortivos tuvieron un efecto similar en los marcadores bioquímicos después de un año de tratamiento. La DMO aumentó significativamente en la cadera total y mostró una tendencia similar en columna lumbar con denosumab, sin diferencias entre ambos tratamientos.

Which is the best antiresorptive treatment after finishing teriparatide? / ¿Cuál es el mejor tratamiento antirresortivo luego de terminar con teriparatide?

Abstract Anabolic drugs are the treatment of choice for osteoporotic patients with very high risk of fractures. Post anabolic treatment with an antiresorptive drug maintains the bone mineral density (BMD) gained. The recommendations regarding the ideal antiresorptive drug are not precise. The aim of this paper is to compare the usefulness of zoledronate and denosumab in a group of 28 women with very high risk of fractures. All of them completed at least one year of treatment with teripatide and latter 14 received zolendronate and 14 denosumab for another year. We retrospectively review their biochemical and densitometric changes. Both treat ment groups experienced a reduction in bone turnover markers of the same magnitude at the end of the second year. In Lumbar Spine BMD increase of 3.96 ± 8.56% Median (Me) 2.54 p = 0.21 in zolendronate group and 3.55 ± 5.36% (Me 5.14) p = 0.07 in denosumab group. Femoral Neck BMD changed -0.09 ± 6.50% (Me 0.29) p = 0.85 in zolendronate group, and - 3.41 ± 5.08% (Me 5.35) p = 0.59 in denosumab group, with no difference between both groups. In Total Hip BMD an increase of 0.55 ± 4.20% (Me 0.43) p = 0.70 in zoledronate group, and 4.53 ± 5.13% (Me 0.64) p = 0.04 with denosumab. We conclude that both antiresortive treatments have a similar effect in biochemical markers after one year of treatment. BMD increase significantly in total hip and changed with a trend toward in lumbar spine with denosumab, but without differences between both groups of treatment.

Resumen Los anabólicos son el tratamiento de elección en la osteoporosis con muy alto riesgo de fracturas. Después del tratamiento anabólico un fármaco antirresortivo mantiene la densidad mineral ósea (DMO) ganada. Las reco mendaciones sobre el fármaco antirresortivo ideal no son precisas. El objetivo de este trabajo es comparar la utilidad de zoledronato y denosumab en un grupo de 28 mujeres con muy alto riesgo de fracturas. Todas ellas completaron al menos un año de tratamiento con teripatide y luego 14 recibieron zolendronato y 14 denosumab durante un año. Revisamos retrospectivamente sus cambios bioquímicos y densitométricos. Ambos grupos de tratamiento experimentaron una reducción de los marcadores de recambio óseo de la misma magnitud al final del segundo año. En columna lumbar la DMO aumentó 3.96 ± 8.56% Mediana (Me) 2.54, p = 0.21 en el grupo zolendronato y 3.55 ± 5.36% (Me 5.14) p = 0.07 en el grupo denosumab. La DMO del cuello femoral cambió -0.09 ± 6.50% (Me 0.29) p = 0.85 en el grupo zolendronato y - 3.41 ± 5.08% (Me 5.35) p = 0.59 en el grupo de denosumab, sin diferencias entre ambos grupos. En la Cadera Total la DMO aumentó 0.55 ± 4.20% (Me 0.43) p = 0.70 con zoledronato y 4.53 ± 5.13% (Me 0.64) p = 0.04 con denosumab. Concluimos que ambos tratamien tos antiresortivos tuvieron un efecto similar en los marcadores bioquímicos después de un año de tratamiento. La DMO aumentó significativamente en la cadera total y mostró una tendencia similar en columna lumbar con denosumab, sin diferencias entre ambos tratamientos.

Sarcopenia in hemodialysis patients from Buenos Aires, Argentina.

OBJECTIVES: Sarcopenia is the loss of skeletal muscle mass and function that occurs with aging that can lead to greater morbidity and mortality. Chronic kidney disease and hemodialysis (HD) favors the development of sarcopenia. We studied the prevalence of sarcopenia and its components using European Working Group on Sarcopenia in Elderly People 2 proposed criteria and risk factors for its development in HD patients. METHODS: In 100 adult HD patients, we evaluated: hand grip strength (HGS), muscle mass by dual energy X-ray absorptiometry and physical performance (gait-speed and sit-stand test). RESULTS: Sixty patients were male and 40 were female; mean age 55.6 years. Prevalence of sarcopenia was 16% (11.1% in males and 25% in females; P = 0.05); 7% had severe sarcopenia. Prevalence of low HGS was 33% in males and 28% in females; low muscle mass was 30% in males but 70% in females and low physical performance 23% in males and 45% in females. Falls were reported by 23 patients. Patients with lower HGS had a higher prevalence of falls in the last year (40% two or more falls; P = 0.03). Only females with sarcopenia had lower bone mineral content. Neither age, body mass index, time on dialysis, or prevalence of diabetes predicted sarcopenia. CONCLUSIONS: A significant proportion of dialysis patients had sarcopenia, more frequent in females. Low HGS was associated with a higher prevalence of falls. Only females with sarcopenia had lower bone mineral content.

Diagnosis and Management of Tumor-induced Osteomalacia: Perspectives From Clinical Experience.

PURPOSE: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome of abnormal phosphate and vitamin D metabolism caused by typically small endocrine tumors that secrete fibroblast growth factor 23 (FGF23). TIO is characterized clinically by progressive musculoskeletal pain, fatigue, proximal muscle weakness, and multiple fractures, leading to long-term disability. Misdiagnosis and delayed diagnosis are common because of the nonspecific symptoms, and several years may elapse before patients receive an accurate diagnosis and appropriate treatment. Thus, it is vital that awareness of the appropriate recognition and management of TIO is increased among healthcare professionals who may encounter patients with suspected TIO. METHODS: A roundtable meeting was held on 10 January 2020 in Dallas, TX, USA, to gather perspectives on the diagnosis and treatment of TIO. The following topics were considered: clinical presentation, patient history, differential diagnosis, laboratory assessment, imaging, venous sampling, and treatment. RESULTS: This report provides a summary of our collective experiences in the management of TIO. MAIN CONCLUSIONS: Laboratory tests are mandatory to expedite TIO diagnosis and should include measurement of fasting serum phosphorus, renal phosphate reabsorption, serum 1,25-dihydroxyvitamin D, and serum FGF23 levels. Functional and anatomical imaging are essential to locate the FGF23-secreting tumor(s) causing TIO. Surgical resection is often a curative treatment when the tumor can be localized; however, better management of patients who cannot be operated on with targeted therapies is needed. Further efforts to increase awareness of TIO within the medical community, and education on recommended diagnostic and treatment pathways are required to improve the management of this debilitating disease.

Impaired bone microarchitecture and strength in patients with tumor-induced osteomalacia.

Some studies based on bone biopsy have demonstrated that in patients with tumor-induced osteomalacia (TIO) the mineralization process of the bone matrix is profoundly disturbed. However, the interrelationship between clinical and biochemical features and bone microarchitecture in this disease needs further analysis. With this purpose in mind, we set out three objectives: (i) to determine bone microarchitecture and estimated bone strength in a group of patients with tumor-induced osteomalacia using high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA), (ii) to investigate correlations between duration of disease, biochemical features, bone density, HR-pQCT and FEA parameters, and (iii) to compare HR-pQCT and FEA parameters with a healthy control group. Ten patients with TIO were included. All patients had non-resolved disease. At the distal radius, all bone microarchitecture parameters were significantly affected in patients with TIO in comparison with healthy controls. At the distal tibia, all parameters were significantly impaired, except for trabecular thickness. All the parameters were more affected in the distal tibia than in the distal radius. Women with TIO (n = 7) had significantly lower bone strength parameters than healthy controls. In men (n = 3), bone strength parameters were significantly lower than in the control group at the distal tibia. Alkaline phosphatase levels exhibited a negative correlation with microarchitecture parameters, failure load, and stiffness. Higher levels of parathyroid hormone correlated with poorer microarchitecture parameters. We believe that in TIO, hormonal disturbances and the lack of mechanical stimulus specially converge to generate an extremely harmful combination for bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).

Severe Bone Microarchitecture Impairment in Women With Pregnancy and Lactation-Associated Osteoporosis.

CONTEXT: Pregnancy- and lactation-associated osteoporosis (PLO) is a rare condition characterized by fragility fractures, mostly vertebral, during the third trimester of pregnancy or the early postpartum period. OBJECTIVE: The aim of this study was to evaluate bone microarchitecture in women with PLO to better understand the pathophysiology of this disease. METHODS: In this retrospective study, we included women with PLO referred to our bone center between November 2007 and July 2012. We assessed bone mineral density (BMD) by dual-energy x-ray absorptiometry, bone turnover markers, and bone microarchitecture by high-resolution peripheral quantitative computed tomography. Results were compared with a control group of healthy lactating women. RESULTS: Of the 7 primiparous patients with PLO, 6 suffered vertebral fractures and 1 developed a hip fracture during the seventh month of gestation. Fractures occurred within the eighth month of pregnancy and the fourth month post partum; vertebral fractures were multiple in 85.7%. Major or minor risk factors for osteoporosis were present in 86% of our patients. Trabecular density, number, and thickness were 34%, 20% and 22% lower than controls (P < .01, P = .01, and P = .01, respectively). Cortical parameters were also deteriorated but to a lesser extent. CONCLUSION: In comparison with healthy lactating women, patients with PLO presented severe deterioration of bone trabecular and cortical microarchitecture. This significant compromise may explain the occurrence of multiple fractures in these otherwise healthy young women. Further prospective studies are needed to determine whether bone microarchitecture might be able to be restored in the future.

Postmenopausal women with sarcopenia have higher prevalence of falls and vertebral fractures / Las mujeres postmenopáusicas con sarcopenia tienen mayor prevalencia de caídas y fracturas vertebrales

Abstract Recently, a new consensus of the European Working Group on Sarcopenia in Older People (EWSOP2) recommended new cut-off points for the diagnosis of sarcopenia. The aim of the present manuscript was to assess the prevalence of sarcopenia in postmenopausal women and its relationship with bone mineral density, falls and fragility fractures according to EWGSOP2. In this cross-sectional study, 250 ambulatory postmenopausal women over 60 years of age were included. Lumbar spine and hip bone mineral density (BMD) and whole-body composition were assessed by dual-energy X-ray absorptiometry (DXA). Muscle strength was evaluated by handgrip dynamometry and physical performance by a 4-m walk gait speed and five-repetition sit-to-stand test. Sarcopenia was defined according to EWGSOP2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass index by DXA). A sarcopenia prevalence of 4% was found in the whole group increasing with age being 12.5% in ≥ 80year-old. A higher percentage of falls, prevalence of osteoporosis and vertebral fractures were found in the sarcopenic group. Sarcopenia increased 6.0-fold the likelihood of having a fragility fracture. Women with sarcopenia had significantly lower femoral neck BMD and higher frequency of falls and vertebral fractures. According to our results, identifying patients with sarcopenia might be a useful tool to detect adults at higher risk of falls and fractures.

Resumen Recientemente el grupo de trabajo europeo sobre sarcopenia en adultos mayores (EWGSOP2) recomendó nuevos criterios y valores de referencia para el diagnóstico de sarcopenia. El objetivo del presente trabajo fue evaluar la prevalencia de sarcopenia en mujeres postmenopáusicas en nuestro medio y su relación con densidad mineral ósea, caídas y fracturas por fragilidad. Este es un estudio de diseño transversal en el cual se incluyeron un total de 250 mujeres ambulatorias mayores de 60 años. La densidad mineral ósea (DMO) de columna lumbar y cadera y la composición corporal fueron evaluados por absorciometría dual de rayos X (DXA). La fuerza fue evaluada por dinamometría de puño; para el rendimiento físico se utilizó caminata de 4 m y la prueba de levantarse y sentarse de una silla (5 repeticiones). La sarcopenia se definió de acuerdo a EWGSOP2 como baja fuerza muscular (dinamometría) y baja masa muscular (índice de masa muscular esquelética por DXA). El 4% de las mujeres cumplía con los criterios de sarcopenia siendo aún mayor en aquellas ≥ 80 años. Las mujeres con sarcopenia presentaron significativamente mayor frecuencia de caídas, osteoporosis y fracturas vertebrales. El riesgo de fracturas por fragilidad se vio incrementado 6 veces en las mujeres con sarcopenia. El diagnóstico de sarcopenia podría considerarse una herramienta útil para identificar a aquellos adultos con riesgo incrementado de caídas y fracturas.

Burden of Disease in Patients With Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a chronic condition associated with muscle weakness and long-term disability. We conducted a cross-sectional study of patients diagnosed with TIO who had been referred to our institution between May 2018 and December 2019. Our aim was to assess health-related quality of life (HRQoL), fatigue, pain, and muscle mass and strength in these patients. Detailed information was obtained regarding general characteristics, initial symptoms and biochemical parameters measured at diagnosis and on the first visit to our institution. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, pain using the Brief Pain Inventory-Short Form (BPI-sf) scale and HRQoL by the 36-item Short Form survey (SF-36) questionnaire. Eight patients were included in the study: three without tumor localization, four with nonremission after surgery, and one with clinical recurrence 2 years after surgery. Fatigue experienced by patients with TIO was significantly higher compared to the general population (p ˂ .0001). The physical summary measure of the SF-36 showed significantly lower values than those of the Argentinean population with chronic conditions (mean 20.4 versus 45.9, p < .0001). According to the BPI-sf, patients with TIO have moderate average pain and the pain interferes severely with walking, general activities, work, and mood. Seven patients had a diagnosis of sarcopenia, four of which had severe sarcopenia. To our best knowledge, this is the first study aimed to quantify fatigue, pain, HRQoL, and muscle mass and strength in a group of patients with TIO. We hope our results contribute to a better understanding of the burden of disease and to establish a basis for future studies-with larger samples-which will make it possible to assess the efficacy of therapeutic interventions for these conditions. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.