Increased Imminent Fracture Risk in Liver Transplant Recipients Despite Bisphosphonate Therapy.

BACKGROUND: Bone loss is significant after orthotopic liver transplant (OLT) and is associated with increased fracture risk and decreased quality of life. In post-transplant fracture prevention, the cornerstone of therapeutic management is bisphosphonates. METHODS: We conducted a retrospective study in a cohort of 155 OLT recipients who received a bisphosphonate prescription at hospital discharge between 2012 and 2016 to investigate post-OLT fragility fracture incidence and predictive risk factors. RESULTS: Before OLT, 14 patients presented a T score < -2.5 SD, and 23 patients (14.8%) had a history of fracture. During follow-up, the cumulative incidence of fractures on bisphosphonates (99.4% risedronate/alendronate) was 9.7% at 12 months and 13.1% at 24 months. The median time to first fragility fracture was 10 months (IQR, 3-22 months) and thus within the first 2 years of follow-up. Predictive factors of fragility fractures in multivariate Cox regression analyses included age 60 years or older (hazard ratio [HR], 2.61; 95% CI, 1.14-6.01; P = .02), post-transplant diabetes mellitus (HR, 3.82; 95% CI, 1.55-9.44; P = .004), and cholestatic disease (HR, 5.93; 95% CI, 2.30-15.26; P = .0002). Additionally, the female sex was associated with a strong trend toward increased fracture risk in univariate analysis (HR, 2.27; 95% CI, 1.00-5.15; P = .05), as well as a post-transplant absolute decrease in bone mineral density at the femoral neck and total hip (P = .08). CONCLUSIONS: This real-world study reports a high incidence of fractures post-OLT despite bisphosphonate therapy. Age 60 years or older, post-transplant diabetes mellitus, cholestatic disease, female sex, and femoral neck and/or total hip bone mineral density loss contribute to increased imminent fracture risk in liver transplant recipients.

Fracture Risk Following an Atypical Femoral Fracture.

Atypical femoral fractures (AFFs) occurring during the course of osteoporosis treatment usually lead to discontinuation of anti-resorptive (AR) drugs. However, the risk of fracture after an AFF is unknown. We conducted a follow-up study of patients with AFF matched 1:3 for age and gender with patients with a peripheral major osteoporotic fracture (pMOF), in the setting of a fracture liaison service, to investigate the incidence of subsequent low-trauma fractures. Fifty-five patients with AFF (95% women, age [mean ± standard deviation] 75 ± 10 years, 89% exposed to AR drugs), followed for 6.2 ± 3.7 years, were compared to 165 matched controls with a pMOF (hip 85%) followed for 4.3 ± 2.6 years. During the follow-up, 38% of patients in the AFF group and 16% in the pMOF group received AR therapies. Continuation of AR drugs after an AFF was associated with contralateral AFF in 27% of subjects. The risks of new low-trauma, major osteoporotic and imminent (within 2 years) fractures, were similar between the two groups: incidence rate ratio (95% confidence interval [CI]) of subsequent fracture following AFF relative to pMOF, 1.30 (95% CI, 0.82-2.04), 1.28 (95% CI, 0.74-2.15), and 1.11 (95% CI, 0.54-2.15), respectively. Moreover, the risk of sustaining multiple fractures per participant was significantly increased among patients with AFF compared to pMOF (hazard ratio 1.48 [95% CI, 1.00-2.19]; p = 0.049). When taking mortality into account, the risk of subsequent fractures tended to be higher in the AFF group (sub-hazard ratio 1.42 [95% CI, 0.95-2.12]). In conclusion, patients who sustained an AFF are at high risk of subsequent fragility fractures, at least equal or even greater to the risk observed after a pMOF. However, continuation of AR drugs increases the risk of contralateral AFF. Therefore, optimal modalities for secondary fracture prevention after AFF require further evaluation. © 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).

Sarcopenia in Chronic Kidney Disease: A Scoping Review of Prevalence, Risk Factors, Association with Outcomes, and Treatment.

Sarcopenia, a condition characterized by loss of skeletal muscle mass and function, has important clinical ramifications. We aimed to map the existing literature about prevalence, risk factors, associated adverse outcomes, and treatment of sarcopenia in individuals with chronic kidney disease (CKD). A scoping review of the literature was conducted to identify relevant articles published from databases' inception to September 2019. Individuals with CKD, regardless of their disease stage and their comorbidities, were included. Only studies with sarcopenia diagnosed using both muscle mass and function, based on published consensus definitions, were included. For studies on treatment, only randomized controlled trials with at least one sarcopenia parameter as an outcome were included. Our search yielded 1318 articles, of which 60 from were eligible for this review. The prevalence of sarcopenia ranged from 4 to 42% according to the definition used, population studied, and the disease stage. Several risk factors for sarcopenia were identified including age, male gender, low BMI, malnutrition, and high inflammatory status. Sarcopenia was found to be associated with several adverse outcomes, including disabilities, hospitalizations, and mortality. In CKD subjects, several therapeutic interventions have been assessed in randomized controlled trial with a muscle mass, strength, or function endpoint, however, studies focusing on sarcopenic CKD individuals are lacking. The key interventions in the prevention and treatment of sarcopenia in CKD seem to be aerobic and resistance exercises along with nutritional interventions. Whether these interventions are effective to treat sarcopenia and prevent clinical consequences in this population remains to be fully determined.

[PTH-replacement therapy in hypoparathyroidism : what benefits ?] / Traitement hormonal substitutif de l'hypoparathyroïdie : quels bénéfices ?

Hypoparathyroidism is a rare disease. In the last decade, important publications have described clinical disease progression and long-term complications. Furthermore, this condition has benefited from major therapeutic advances with the emergence of a hormonal substitution therapy with injectable parathyroid hormone, rhPTH (1-84) (Recombinant human parathyroid hormone, 1-84). Conventional therapy, with calcium supplements and active vitamin D analogue, is effective but does not always fulfill all therapeutic targets and is associated with hypercalciuria. In most patients, therapy with rhPTH (1-84) is associated with a substantial reduction of at least 50% in the need for calcium and active vitamin D along with maintenance of serum calcium. Additionally, rhPTH (1-84) is associated with decreased in 24h urinary calcium excretion with preservation of renal function, which can be a major asset.

L'hypoparathyroïdie est une maladie rare. Au cours de la dernière décennie, d'importantes publications ont décrit son évolution et ses complications à long terme. Cette maladie a également bénéficié d'avancées majeures sur le plan thérapeutique avec l'avènement d'un traitement substitutif à base de parathormone injectable, la rhPTH (1-84) (hormone parathyroïdienne 1,84 recombinante). La thérapie conventionnelle à base de suppléments calciques et de vitamine D active est efficace, mais ne permet pas toujours d'atteindre les objectifs thérapeutiques et est associée à l'hypercalciurie. La rhPTH (1-84) aide à maintenir une calcémie dans la cible en diminuant d'au moins 50 % les doses de calcium et de vitamine D active. De plus, elle est associée à une diminution de la calciurie de 24 heures avec une préservation de la fonction rénale, ce qui peut constituer un atout majeur.

[Osteoporosis: Novel drug, new recommendations]. / Ostéoporose - Nouvelle molécule, nouvelles directives.

New recommendations from the Swiss Association against Osteoporosis (SVGO) concerning fracture risk stratification and treatment delineate two new risk categories : very high risk (FRAX 10-years probability of fracture at least 20 % above the usual intervention threshold) and imminent risk (major osteoporotic fracture in the last 2 years). In these patients, parenteral therapies are recommended first. Among them, romosozumab is now available in Switzerland and is indicated for 1 year in absence of cardiovascular contra-indications, followed by an anti-resorptive. Regarding denosumab, several studies indicate that post-treatment bone loss may be, at least partially, prevented by zoledronate. Finally, monitoring BMD changes and the T-score reached on any therapy could be used as an indicator of anti-fracture efficacy.

Les nouvelles directives de l'Association suisse contre l'ostéoporose proposent deux nouvelles catégories dans la stratification du risque fracturaire et du traitement : très haut risque (FRAX au moins 20 % au-dessus du seuil d'intervention pour l'âge) et risque imminent (fracture ostéoporotique majeure au cours des 2 dernières années). Chez ces patient·e·s, les thérapies parentérales sont indiquées en première intention. Parmi celles-ci, le romosozumab est maintenant disponible en Suisse et est indiqué pour 1 an en l'absence de contre-indication cardiovasculaire, suivi d'un antirésorptif. Concernant le dénosumab, plusieurs études ont démontré que la perte osseuse à l'arrêt peut être, au moins partiellement, prévenue par l'acide zolédronique. Finalement, le score-T atteint sous thérapie pourrait être un indicateur clinique de l'effet antifracturaire.

Hypomagnesemia During Teriparatide Treatment in Osteoporosis: Incidence and Determinants.

In our clinical experience, we have encountered patients who developed hypomagnesemia after the introduction of teriparatide. Some trials have reported hypomagnesemia as an adverse event during teriparatide treatment, but this issue had never been studied specifically. Our objective was twofold: 1) determine the incidence of hypomagnesemia (serum magnesium <0.7 mmol/L) associated with teriparatide in a retrospective cohort and 2) identify the predisposing factors to hypomagnesemia in this cohort. We reviewed the files of 53 patients treated for severe osteoporosis with teriparatide for 6 to 24 months between May 2008 and January 2016. Serum magnesium levels were measured at 0, 3, 6, 12, 18, and 24 months. In the full cohort, we observed an average decrease of serum magnesium of 0.075 mmol/L, 0.069 mmol/L, 0.085 mmol/L, 0.086 mmol/L (p < 0.001) at 3, 6, 12 months, and at the end of the treatment, respectively. The cumulative incidence of hypomagnesemia during treatment with teriparatide was 35.9% (19 patients). Patients' older age (71.1 versus 65.1 years; p = 0.05) and lower baseline level of magnesium before teriparatide treatment (0.81 mmol/L versus 0.85 mmol/L; p = 0.03) were significant risk factors for teriparatide-induced hypomagnesemia. The average decrease of serum magnesium was greater in the patients who developed hypomagnesemia compared with normomagnesemic patients at 3 months (0.110 mmol/L versus 0.054 mmol/L; p = 0.02), 6 months (0.139 mmol/L versus 0.036 mmol/L; p < 0.001), and 12 months (0.156 mmol/L versus 0.048 mmol/L; p < 0.001). Serum calcium, creatinine, and parathyroid hormone remained normal throughout the treatment period. We observed a statistically significant decrease in the serum magnesium levels in patients treated with teriparatide for severe osteoporosis. Older age and lower baseline magnesium were significant determinants of hypomagnesemia. Closer monitoring of serum magnesium level should be considered in these patients. © 2018 American Society for Bone and Mineral Research.