The association between sarcopenia and osteoporotic vertebral compression refractures Abstract Summary Sarcopenia was reported to be significantly associated with osteoporosis. In this study, we reported for the first time that sarcopenia was an independent risk predictor of osteoporotic vertebral compression refractures (OVCRFs). Other risk factors of OVCRFs are low bone mass density T-scores, female sex, and advanced age. Introduction The purpose of this study was to investigate the association between osteoporotic vertebral compression refractures (OVCRFs) and sarcopenia, and to identify other risk factors of OVCRFs. Methods We evaluated 237 patients with osteoporotic vertebral compression fracture who underwent percutaneous kyphoplasty (PKP) in our hospital from August 2016 to December 2017. To diagnose sarcopenia, a cross-sectional computed tomography (CT) image at the inferior aspect of the third lumbar vertebra (L3) was selected for estimating muscle mass. Grip strength was used to assess muscle strength. Possible risk factors, such as age, sex, body mass index (BMI), bone mineral density (BMD), location of the treated vertebra, anterior-posterior ratio (AP ratio) of the fractured vertebra, cement leakage, and vacuum clefts, were assessed. The multivariable analysis was used to determine the risk factors of OVCRFs. Results During the follow-up period, OVCRFs occurred in 64 (27.0%) patients. Sarcopenia was present in 48 patients (20.3%), including 21 OVCRFs and 27 non-OVCRFs patients. Sarcopenia was significantly correlated with advanced age, lower BMI, lower BMD, and hypoalbuminemia. Compared with non-sarcopenic patients, sarcopenic patients had higher OVCRFs risk. In univariate analysis, sarcopenia (p = 0.003), female (p = 0.024), advanced age (≥ 75 years; p < 0.001), lower BMD (p < 0.001), lower BMI (p = 0.01), TL junction (vertebral levels at the thoracolumbar junction) (p = 0.01), cardiopulmonary comorbidity (p = 0.042), and hypoalbuminemia (p = 0.003) were associated with OVCRFs. Multivariable analysis revealed that sarcopenia (OR 2.271; 95% CI 1.069–4.824, p = 0.033), lower BMD (OR 1.968; 95% CI 1.350–2.868, p < 0.001), advanced age (≥ 75 years; OR 2.431; 95% CI 1.246–4.744, p = 0.009), and female sex (OR 4.666; 95% CI 1.400–15.552, p = 0.012) were independent risk predictors of OVCRFs. Conclusions Sarcopenia is an independent risk predictor of osteoporotic vertebral compression refractures. Other factors affecting OVCRFs are low BMD T-scores, female sex, and advanced age.

Elderly males with or without existing osteoporotic vertebral fracture have much lower future vertebral fracture risk than elderly females: the MrOS (Hong Kong) year-4 follow-up spine radiograph study Abstract Summary MrOS (Hong Kong)’s year-4 follow-up shows, for subjects at baseline without vertebral deformity (VD) and endplate or/and cortex fracture (ECF), the VD progression/new VD rate during follow-up in males was half of our paired MsOS (Hong Kong) study’s results. For those with VD or ECF, the VD progression/new VD was less than one sixth of females’ rate. Introduction This study documents MrOS (Hong Kong)’s year-4 follow-up, and the results are compared with the MsOS (Hong Kong) study. Of elderly females with Genant’s grade-0, -1, -2, and -3 VD, at year-4 follow-up, 4.6%, 8%, 10.6%, and 28.9% had at least one VD progression or incident VD, respectively. Methods Spine radiographs of 1500 Chinese males with baseline (mean age 71.7 years, range 65–91 years) and year-4 follow-up were evaluated according to Genant’s VD criteria and ECF (non-existent, ECF0; or existent, ECF1). Grade-2 VDs were divided into mild (VD2m, 25–34% height loss) and severe (VD2s, 34–40% height loss) subgroups. Study subjects were graded into eight categories: VD0/ECF0, VD1/ECF0, VD2m/ECF0, VD0/ECF1, VD1/ECF1, VD2m/ECF1, VD2s/ECF1, and VD3/ECF1. With an existing VD, a further height loss of ≥ 15% was a VD progression. A new VD incident was a change from grade-0 to grade-2/3, or to grade-1 with ≥ 10% height loss. Results Of subjects with Genant’s grade-0, 2.05% (25/1219) developed at least one VD progression or/and new VD, while of subjects with Genant’s grade-1, -2, and -3 VD, only 2% (3/149), 3.1% (3/96), and 2.8% (1/36) developed at least one VD progression/new VD, respectively. Among the three ECF0 groups, there was a significant difference in new ECF incidence, with VD0/ECF0 being the lowest and VD2m/ECF0 being the highest. Conclusion VD progression/new VD is much less common in elderly men than in elderly women. Vertebrae with VD had a higher risk of developing ECF.

Correction to: Secondary prevention of osteoporotic fractures: evaluation of the Lille University Hospital’s Fracture Liaison Service between January 2016 and January 2018 The original version of this article, published on 5 June 2019, an author’s name was misspelled.

Correction to: The factor-of-risk biomechanical approach predicts hip fracture in men and women: the Framingham Study The original version of this article, published 23 February 2011, unfortunately contained a mistake. The following correction has therefore been made in the original:

Correction to: Prevalent vertebral fractures and minor vertebral deformities analyzed by vertebral fracture assessment (VFA) increases the risk of incident fractures in postmenopausal women: the FRODOS study Figure 1 as published in the original version of this article was unfortunately incomplete.

Diffuse, fracturing systemic skeletal histiocytosis of unknown type: a novel metabolic bone disease Abstract We describe a novel disease of diffuse skeletal histiocytosis associated with multiple fragility fractures and high osteoclast activity. Clinical, radiographic, biochemical, genetic, and histopathological investigations were performed to characterize the diagnosis of an Asian man who presented with hip fracture and diffuse skeletal lytic lesions. After excluding malignancy and other common metabolic bone diseases, open bone biopsy yielded several pathological samples all showing extensive skeletal histiocytosis likely to explain the diffuse axial and appendicular lytic lesions. Rare disorders such as Langerhans histiocytosis, Erdheim-Chester disease, and diffuse cystic skeletal angiomatosis were excluded through careful pathological examination and lack of CD1a and S-100 staining. Whole exome sequencing did not yield diagnostic findings to explain this likely acquired disease. High markers of osteoclast activity suggested excessive focal bone resorption but normalized after zoledronic acid treatment. A novel disease of skeletal histiocytosis with high bone turnover is differentiated from other histiocytic and lytic skeletal diseases.

Hypophosphatasia: Canadian update on diagnosis and management Abstract Summary Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism caused by loss of function mutations in the ALPL gene. The presentation in children and adults can be extremely variable and natural history is poorly understood particularly in adults. Careful patient evaluation is required with consideration of pharmacologic intervention in individuals meeting criteria for therapy. Introduction The purposes of this review are to present current evidence regarding the diagnosis and management of hypophosphatasia in children and adults and provide evidence-based recommendations for management. Method A MEDLINE, EMBASE, and Cochrane database search and literature review was completed. The following consensus recommendations were developed based on the highest level of evidence as well as expert opinion. Results Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism due to loss of function mutations in the tissue non-specific alkaline phosphatase (ALPL) gene causing reductions in the activity of the tissue non-specific isoenzyme of alkaline phosphatase (TNSALP). Deficient levels of alkaline phosphatase result in elevation of inhibitors of mineralization of the skeleton and teeth, principally inorganic pyrophosphate. The impaired skeletal mineralization may result in elevations in serum calcium and phosphate. Clinical features include premature loss of teeth, metatarsal and subtrochanteric fractures as well as fragility fractures. Poor bone healing post fracture has been observed. Myalgias and muscle weakness may also be present. In infancy and childhood, respiratory and neurologic complications can occur. Conclusions HPP is associated with significant morbidity and mortality. Pharmacologic intervention can result in significant clinical improvement. This Canadian position paper provides an overview of the musculoskeletal, renal, dental, respiratory, and neurologic manifestations of hypophosphatasia. The current state of the art in the diagnosis and management of hypophosphatasia is presented.

Fracture risk following intermission of osteoporosis therapy Abstract Summary Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped. Introduction The aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab. Methods Systematic review. Results Differing pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20–40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture. Conclusions The view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare.

Efficacy and safety of elcatonin in postmenopausal women with osteoporosis: a systematic review with network meta-analysis of randomized clinical trials Abstract Summary The present systematic review aimed to evaluate bone mineral density (BMD) change and complication rates of elcatonin on treating postmenopausal osteoporosis. The result confirmed efficacy of elcatonin and safety in combination therapies of elcatonin (C-E). Introduction Postmenopausal osteoporosis is an important issue in global aging trends. One treatment of osteoporosis is elcatonin, a kind of calcitonin. However, it has been challenged for long time because of safety. Many trials investigated on this topic, but they were designed differently. Those designs can be categorized in monotherapy of elcatonin (M-E) and C-E. Unfortunately, no synthesized evidence dealt this topic. Methods This study systematically identified target trials from six important databases and only included randomized controlled trial for synthesis. Two investigators assessed quality of eligible trials using the Cochrane Risk of Bias Tool, and they independently extracted data. Network meta-analysis performed Peto odds ratio (POR, used for dealing with zero cell) or weighted mean difference (WMD, for continuous data) with 95% confidence intervals (CI) and consistency H. Results Sixteen trials recruiting 2754 women with postmenopausal osteoporosis were included in our study. Elcatonin therapies and non-elcatonin medications had comparable fracture rates and bone mineral density change. Yet, C-E (WMD, − 18.93; 95% CI, − 23.97 to − 13.89) and M-E (WMD, − 13.72; 95% CI, − 19.51 to − 7.94) had significantly lower pain score than non-elcatonin medications. However, M-E (POR = 8.413, 95% CI, 2.031 to 34.859) and non-elcatonin medication (Peto OR, 7.450; 95% CI, 1.479 to 37.530) had significantly higher complication rates than placebo. No evidence detected inconsistency and small study effect in this network model. Conclusions Based on current evidence, C-E may be considered for treating postmenopausal osteoporosis because it benefits on pain relief and complications. Moreover, it shows comparable fracture rate and bone mineral density change as compared with anti-osteoporosis and calcium supplements. Nevertheless, further trials are needed to investigate formula and dosages of elcatonin.

Two-year persistence with teriparatide improved significantly after introduction of an educational and motivational support program Abstract Summary This study evaluated the 2-year persistence with teriparatide in the Netherlands. Analyses showed that the risk of non-persistence was 28% lower in patients who were followed according to an additional educational and motivational support program. Introduction Until recently, teriparatide (TPTD) was a third-line treatment option for severe osteoporosis in the Netherlands, which could only be prescribed by medical specialists based on a specific medical statement. We aimed to determine whether an educational and motivational support program (EMSP) increased 2-year treatment persistence with TPTD in patients with severe osteoporosis. Methods We evaluated persistence in 1573 Dutch patients treated with TPTD from January 2013 until January 2018. From January 2013 onwards, all patients received a basic support program (BSP) consisting of an educational home visit to initiate TPTD treatment and phone calls (at 1, 2.5 and 8 weeks). Since May 2015, all patients received the EMSP consisting of the BSP extended with evaluation of medication adherence during phone calls, an additional phone call (at 12 months), and motivational letters at 9 and 14 months. Results The EMSP showed a statistically significantly higher 2-year persistence (78%) with TPTD as compared with the BSP (72%). Reasons for treatment discontinuation were comparable between groups, except for the proportion of patients who had stopped TPTD administration due to side effects, which was significantly lower in the EMSP group (8% vs. 15% in BSP, p < 0.001). Overall, the risk of non-persistence was 28% lower in the EMSP compared with the BSP group (HR: 0.72; 95% CI: 0.55–0.93). Conclusion The introduction of the EMSP has demonstrated to improve the persistence with TPTD, resulting in 78% of the patients being persistent with TPTD during the 2-year treatment period.