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Texture Research Imaging Platform applies trabecular bone score (TBS) measurement principles to images acquired with multiple modalities to assess bone texture at various skeletal sites. This study aimed to assess the bone texture score in dual-energy X-ray absorptiometry-acquired lateral vertebral fracture assessment (VFA) images (BTS

Aims Maximal exercise capacity as measured by peak oxygen consumption (pVO2) in cardiopulmonary exercise testing (CPET) of heart transplant recipients (HTR) is limited to a 50–70% level of healthy age‐matched controls. This study investigated the relationship between body composition and pVO2 during the first decade post‐transplant. Methods and results Body composition was determined by dual‐energy X‐ray absorptiometry (DXA) and pVO2 by CPET in 48 HTR (n = 38 males; mean age 51 ± 12 years). A total of 95 assessments were acquired 1–9 years post‐transplant, and the results of four consecutive periods were compared [Period 1: 1–2 years (n = 25); 2: 3–4 years (n = 23); 3: 5–6 years (n = 23); 4: 7–9 years (n = 24)]. Linear regression analysis analysed the correlation between pVO2 and pairs of appendicular lean mass (ALM) and fat mass (FM). The relation between ALM and daily dose of calcineurin inhibitor (CNI) was explored using partial correlation controlling for age, gender, and height. pVO2 increased from 0.98 (0.34) to 1.35 (0.35) L/min (P 8.8 kg/m2). ALM normalized to body mass index increased from 0.690 (0.188) to 0.848 (0.204) m2 (P = 0.02) between Periods 1 and 4, explaining 45% of the variance of pVO2 (R 2 = 0.455; P

A rebound of osteoclast activity during the 2 years after a treatment or prevention of osteoporosis with denosumab (Dmab) leads to an increased risk of vertebral fractures (VFs). We attempted to identify the risk factors for these VF and to examine the protective role of bisphosphonates. For that, 22 specialists in Switzerland provided data of unselected patients, treated with denosumab for osteoporosis or breast cancer without metastases under aromatase inhibitors, who have received at least two injections of Dmab, with at least 1 year of follow‐up after discontinuation. The questionnaire covered separately the periods before, during, and after Dmab treatment, and registered clinical, radiological, and lab data. For the analysis of the risk factors, the main outcomes were the time to the first VF after the treatment, the presence of multiple VFs (MVFs), and the number of VFs. The incidence of VF was 16.4% before, 2.2% during, and 10.3% after the treatment with Dmab. The risk of VF after Dmab discontinuation was associated with an increased risk of non‐vertebral fractures. The pretreatment predictors of the post‐treatment fracture risk were a parental hip fracture and previous VFs. Further risk factors appeared later, such as low total hip bone mineral density (BMD) during and after denosumab, increased bone resorption markers, and the loss of total hip BMD after the denosumab. Treatment with bisphosphonates, especially after Dmab, had a protective effect. Bisphosphonates given before Dmab did not further decrease the risk of VF in cases who got bisphosphonates after Dmab. This study shows that the risk of VF is poorly predictable before the prescription of denosumab. But during and after the treatment, bone resorption markers and BMD have a significant predictive value. Bisphosphonates after the treatment with denosumab are protective against VFs. © 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).

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/., Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration., Open access funding provided by University of Geneva

Denosumab discontinuation is associated with a rapid increase in bone resorption and a decrease in bone mineral density. Spontaneous vertebral fractures may occur as a side effect of the rebound of bone resorption. Cases of rebound-linked hypercalcemia have also been described, moderate in women with osteoporosis and breast cancer and severe in children receiving oncological doses of denosumab. We report the case of an adult woman with primary hyperparathyroidism and moderate hypercalcemia, treated with denosumab for osteoporosis, who developed severe hypercalcemia and spontaneous vertebral fractures (SVFs) after denosumab discontinuation. An 86-year-old woman with densitometric osteoporosis was treated for 3 years with 60 mg of subcutaneous denosumab every 6 months. She was known to have primary hyperparathyroidism, with a serum albumin-corrected calcium of 2.82 mmol/l (NV 2.15-2.5) at the end of denosumab effect. Nine months after the last denosumab injection, she was hospitalized due to worsening overall health. Clinical evaluation revealed severe hypercalcemia (calcium 3.35 mmol/l). Very high values of bone turnover markers (BTMs) suggested a rebound effect due to denosumab discontinuation. An X-ray showed multiple new SVFs. After injection of denosumab 60 mg, serum calcium rapidly decreased and BTMs were dramatically reduced. A surgical approach by minimally invasive parathyroidectomy allowed for definite resolution of hyperparathyroidism and hypercalcemia. This case suggests that hypercalcemia can be a side consequence of denosumab discontinuation, which can become severe when other causes of hypercalcemia, such as primary hyperparathyroidism, are present.

Summary Lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) are both calculated on L1-L4 vertebrae. This study investigated the ability to predict osteoporotic fractures of BMD and TBS as calculated based on all possible adjacent L1-L4 vertebrae combinations. Present findings indicate that L1-L3 is an optimal combination to calculate LS-BMD or TBS. Introduction Lumbar spine (LS) BMD and TBS are both assessed in the LS DXA scans in the same region of interest, L1-L4. We aimed to investigate the ability to predict osteoporotic fractures of all the possible adjacent LS vertebrae combinations used to calculate BMD and TBS and to evaluate if any of these combinations performs better at osteoporotic fracture prediction than the traditional L1-L4 combination. Methods This study was embedded in OsteoLaus-women cohort in Switzerland. LS-DXA scans were performed using Discovery A System (Hologic). The incident vertebral fractures (VFs) and major osteoporotic fractures (MOFs) were assessed from VF assessments using Genant’s method or questionnaires (non-VF MOF). We ran logistic models using TBS and BMD to predict MOF, VF, and non-VF MOF, combining different adjustment factors (age, fracture level, or BMD). Results One thousand six hundred thirty-two women (mean ± SD) 64.4 ± 7.5 years, BMI 25.9 ± 4.5 kg/m2, were followed for 4.4 years and 133 experienced MOF. The association of one SD decrease L1-L3 BMD with the odds ratios (ORs) of MOF was OR 1.32 (95%CI 1.15–1.53), L2-L4 BMD was 1.25 (95%CI 1.09–1.42), and L1-L4 BMD was 1.30 (95%CI 1.14–1.48). One SD decrease in L1-L3 TBS was more strongly associated with the odds of having a MOF (OR 1.64, 95% CI 1.34–2.00), than one SD decrease in L2-L4 TBS (OR 1.48, 95% CI 1.21–1.81), or in L1-L4 TBS (OR 1.60, CI 95% 1.32–1.95). Conclusion Current findings indicate that L1-L3 is an optimal combination for the TBS or LS-BMD calculation.

Quantitative ultrasound (QUS) presents a low cost and readily available alternative to DXA measurements of bone mineral density (BMD) for osteoporotic fracture risk assessment. It is performed in a variety of skeletal sites, among which the most widely investigated and clinically used are first the calcaneus and then the radius. Nevertheless, there is still uncertainty in the incorporation of QUS in the clinical management of osteoporosis as the level of clinical validation differs substantially upon the QUS models available. In fact, results from a given QUS device can unlikely be extrapolated to another one, given the technological differences between QUS devices. The use of QUS in clinical routine to identify individuals at low or high risk of fracture could be considered primarily when central DXA is not easily available. In this later case, it is recommended that QUS bone parameters are used in combination with established clinical risk factors for fracture. Currently, stand-alone QUS is not recommended for treatment initiation decision making or follow-up. As WHO classification of osteoporosis thresholds cannot apply to QUS, thresholds specific for given QUS devices and parameters need to be determined and cross-validated widely to have a well-defined and certain use of QUS in osteoporosis clinical workflow. Despite the acknowledged current clinical limitations for QUS to be used more widely in daily routine, substantial progresses have been made and new results are promising.

Osteoporosis is the most common chronic metabolic bone disease, known to be underdiagnosed and undertreated in parts of the Swiss population. Due to expected rise in new fragility fractures, adequate awareness of associated risk factors and diagnostic and therapeutic options will be essential for the management of osteoporosis. We therefore explored these aspects in a nationwide survey of Swiss specialists and their patients. A total of 262 physician questionnaires and 9065 patient questionnaires were analyzed, mainly from general practitioners (64.9%), followed by rheumatologists (16.8%), gynecologists (12.2%), and endocrinologists (6.1%). Around 20% of patients were under medication and/or had a medical condition increasing the risk of osteoporosis. Further risk factors, such as low consumption of calcium-rich foods, smoking, elevated alcohol intake, and insufficient physical activity, were present across regions and medical fields. 53.9% of patients did not take calcium/vitamin D supplements; 3.5% reported having fragility fractures, and 7.3% received treatment for osteoporosis. Only 38.5% of surveyed patients knew of the chronic nature of osteoporosis, indicating rather low awareness in this population. Despite generally perceived relevance of osteoporosis for daily practice, aspects of its prevention and management varied across regions and medical fields. Raising awareness among patients and physicians will be vital for addressing osteoporosis on a national scale.

Context: Denosumab inhibits bone resorption, increases bone mineral density, and reduces fracture risk. Denosumab was approved for the treatment of osteoporosis and the prevention of bone loss in some oncological situations. Denosumab discontinuation is associated with a severe bone turnover rebound (BTR) and a rapid loss of bone mineral density. The clinical consequences of the BTR observed after denosumab discontinuation are not known. Cases Description: We report 9 women who presented 50 rebound-associated vertebral fractures (RAVFs) after denosumab discontinuation. A broad biological and radiological assessment excluded other causes than osteoporosis. These 9 cases are unusual and disturbing for several reasons. First, all vertebral fractures (VFs) were spontaneous, and most patients had a high number of VFs (mean = 5.5) in a short period of time. Second, the fracture risk was low for most of these women. Third, their VFs occurred rapidly after last denosumab injection (9-16 months). Fourth, vertebroplasty was associated with a high number of new VFs. All the observed VFs seem to be related to denosumab discontinuation and unlikely to the underlying osteoporosis or osteopenia. We hypothesize that the severe BTR is involved in microdamage accumulation in trabecular bone and thus promotes VFs. Conclusion: Studies are urgently needed to determine 1) the pathophysiological processes involved, 2) the clinical profile of patients at risk for RAVFs, and 3) the management and/or treatment regimens after denosumab discontinuation. Health authorities, physicians, and patients must be aware of this RAVF risk. Denosumab injections must be scrupulously done every 6 months but not indefinitely.

OsteoLaus: Right to Exist and First Results Abstract. The OsteoLaus cohort included 1475 women aged 50 to 80 years between 2010 and 2012, and since followed every 2.5 years. The main goal is to better define osteoporosis and the prediction of fracture risk. Using the multiple data available in CoLaus/PsycoLaus, many analyses are being conducted to better understand the relationship between bone health and chronic disease.

Regional soft tissue may have a noise effect on trabecular bone score (TBS) and eventually alter its estimate. The current TBS software (TBS iNsight®) is based on an algorithm accounting for body mass index (BMI) (TBSv3.03 ). We aimed to explore the updated TBS algorithm that accounts for soft tissue thickness (TBSv4.0 ). This study was embedded in the OsteoLaus cohort of women in Lausanne, Switzerland. Hip and lumbar spine (LS) dual-energy X-ray absorptiometry (DXA) scans were performed using Discovery A System (Hologic). The incident major osteoporotic fractures (MOFs) were assessed from vertebral fracture assessments using Genant's method (vertebral MOF) or questionnaires (nonvertebral MOF). We assessed the correlations of bone mineral density (BMD) or TBS with body composition parameters; MOF prediction ability of both versions of TBS; and the differences between Fracture Risk Assessment Tool (FRAX) adjusted for TBSv3.03 or TBSv4.0 . In total, 1362 women with mean ± SD age 64.4 ± 7.5 years and mean ± SD BMI 25.9 ± 4.5 kg/m2 were followed for 4.4 years and 132 experienced an MOF. All the anthropometric measurements of our interest were positively correlated with LS, femoral neck, or hip BMD and TBSv4.0 ; whereas with TBSv3.03 their correlations were negative. In the models adjusted for age, soft tissue thickness, osteoporotic treatment, and LS-BMD, for each SD decline in TBSv3.03 , there was a 43% (OR 1.43; 95% CI, 1.12 to 1.83) increase in the odds of having MOF; whereas for each SD decline in TBSv4.0 , there was a 54% (OR 1.54; 95% CI, 1.18 to 2.00) increase in the odds of having an MOF. Both FRAXs were very strongly correlated and the mild differences were present in the already high-risk women for MOF. This study shows that TBSv4.0 overcomes the debatable residual negative correlation of the current TBS with body size and composition parameters, postulating itself as free from the previously acknowledged technical limitation of TBS. © 2019 American Society for Bone and Mineral Research.

At denosumab discontinuation, bone turnover markers increase and the gained BMD is lost. In postmenopausal osteoporosis, there is an increased risk of spontaneous vertebral fractures (VFs) of about 1 to 10%, rarely described in women under denosumab for aromatase inhibitors (AI)-treated breast cancer. We aim to describe the characteristics of 15 patients under denosumab given for AI-treated early-stage breast cancer that presented VFs at its discontinuation. Single-center retrospective case series of 15 patients. We report clinical data, dual X-ray absorptiometry values at denosumab initiation and discontinuation, and serum B-crosslaps dosage at the time of VF occurrence (before denosumab resumption). Fifteen women (66.4 ± 7.1 years at denosumab discontinuation) that received AI for 5.0 ± 0.6 years, denosumab 60 mg for 8.2 ± 2.0 doses, and developed 60 VFs at denosumab discontinuation, were followed for 24.4 ± 9.5 months. Patients suffered from 1 to 11 (mean 4.0 ± 1.9) clinical VFs within 7 to 16 months after last denosumab injection. VFs developed earlier in patients with longer denosumab treatment (R2 = 0.29, p = 0.04) and in patients without osteoporosis before denosumab (9.4 ± 2.0 vs. 13.0 ± 2.0 months; p = 0.005). Serum B-crosslaps at the time of VFs tended to be higher in patients with earlier VFs (R2 = 0.47; p = 0.06) or with longer denosumab treatment (R2 = 0.48; p = 0.06). Denosumab was resumed in all patients, then switched for a bisphosphonate in eight. No new VFs occurred during follow-up. Despite an apparently low fracture risk, women under denosumab for AI-treated early-stage breast cancer develop spontaneous VFs at denosumab discontinuation. This risk increases with treatment duration and may be prevented by a potent bisphosphonate.

OBJECTIVE Transient loss of consciousness (TLOC) is a common presentation in the emergency room, where patient history can usually differentiate syncope from generalized tonic-clonic (GTC) seizures. Several serum markers, such as creatine kinase and lactate, can be helpful, especially when history is unreliable. Here, we explore a potential supporting role of electrolyte plasma levels in a case-control study. METHODS In our electroencephalographic database, we retrospectively identified consecutive episodes of loss of consciousness in adults seen over 3 years in our hospital emergency department for a case-control study. We investigated plasma levels of several electrolytes (sodium, potassium, phosphate, calcium, magnesium) at the emergency visit, as well as demographics, diagnosis, blood-sample delay time, and history of alcohol abuse. RESULTS Of the 126 patients identified, 75 had GTC seizures and 46 had other TLOC causes. Among electrolyte levels, only hypophosphatemia was associated with GTC seizures (median = 0.79 mmol·L-1 , range = 0.34-1.37 in GTC seizures vs 0.93 mmol·L-1 , range = 0.52-1.56, P = 0.001 in TLOC). After adjusting for blood sampling delay, alcohol abuse, and other electrolyte levels, only hypophosphatemia was associated with GTC seizures, occurring in 37 (51%) of GTC seizures and 12 (22%) of other TLOC (odds ratio = 3.5, 95% confidence interval = 1.5-8.3, P = 0.003). Hypophosphatemia < 0.6 mmol·L-1 was 93% specific and 20% sensitive for GTC seizure occurrence. In follow-ups, hypophosphatemia was transitory. SIGNIFICANCE Transient hypophosphatemia is common after GTC seizures and could represent an additional biological marker to help differentiate GTC seizures from other TLOC, especially when history is unclear. This hypothesis needs to be tested prospectively.

ZusammenfassungDie Wechseljahre sind durch tiefgreifende klinische und hormonelle Veränderungen gekennzeichnet. Ein Östrogenmangel führt zu einem beschleunigten Knochenverlust und erhöhtem Frakturrisiko. Parallel dazu deuten Verlaufs-Studien auf einen Anstieg der Adipositas mit einer Neigung zu mehr zentralem Fett sowie einen Verlust an Muskelmasse hin. Die post-menopausale Hormontherapie (MHT), die derzeit auf die symptomatische Linderung von Hitzewallungen und andere klimakterische Symptome beschränkt ist, hat sich als wirksam erwiesen, um die Knochendichte zu erhalten. Jüngste Daten der OsteoLaus-Kohorte, einer bevölkerungsbasierten Studie mit postmenopausalen Frauen im Alter von 50–80 Jahren, deuten darauf hin, dass zusätzlich ein günstiger Effekt auf die Mikroarchitektur der Knochen vermittelt wird. Darüber hinaus haben Frauen unter MHT, weniger androides und viszerales Fett, entsprechend der verfügbaren Daten aus anderen Studien. Die Physiopathologie dieses Zusammenhangs ist nicht vollständig geklärt und kann Änderungen des Energieverbrauchs durch Östrogene betreffen. Im Gegenteil scheint die Wirkung der MHT auf die Magermasse begrenzter zu sein und könnte mit spezifischen Arten MHT oder dem zeitlichen Einsatz der MHT in Verbindung gebracht werden. Interessanterweise ist die Entwicklung nach dem MHT-Entzug in verschiedenen Geweben nicht identisch, wobei der Verlust des Nutzens für das Fettgewebe schneller eintritt. In Anbetracht des erneuten Interesses von MHT, zumindest für Frauen in der frühen Postmenopause, können diese Daten bei der Erwägung einer MHT wertvoll sein.