Development and validation of an eight-item calcium screener to assess daily calcium intake of patients with osteoporosis in clinical practice.

OBJECTIVE: To validate a short food frequency questionnaire (screener) estimating daily average calcium intake from dietary sources to guide calcium supplementation of patients with osteoporosis in clinical practice. METHODS: An eight-item calcium screener was developed based on existing literature, food consumption data and expert opinion. Convergent validity was determined by comparison with 3-day food records using mean difference, Spearman's correlation coefficients (SCC) and Bland-Altman analysis. Test-retest reliability was assessed by SCC and intraclass correlation coefficients (ICC). We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to identify patients requiring calcium supplementation (<1200 mg dietary calcium intake/day). RESULTS: Fifty-two patients filled out the eight-item calcium screener and the 3-day Food record (mean age of 66.8 ± 12.9 (SD)) and 38 patients filled out the screener twice for reliability analysis (mean age of 65.8 ± 12.8 (SD)). Dietary calcium intake between the calcium screener and food records showed a strong correlation (N = 52 patients, SCC = 0.53, p ≤ 0.001) and mean difference of 21 mg (p = 0.70). Bland-Altman analysis showed agreement within 95% confidence intervals for 49/52 comparisons (94%). Test-retest reliability of the calcium screener was excellent (SCC = 0.96, p ≤ 0.001; ICC = 0.99, p ≤ 0.001). CONCLUSION: The calcium screener shows good convergent validity, reliability and feasibility to estimate daily calcium intake of patients with osteoporosis in routine clinical practice.

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.

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

Bone: best papers of the year 2017.

An overview of selected papers related to bone published in 2017 is provided. PURPOSE: This paper accompanies a lecture at the 2018 Belgian Bone Club annual Clinical Update Symposium held in Brussels on January 20th, discussing the best papers (in the opinion of the author) published in the previous year. METHODS: A PubMed search using the keyword "bone" and articles published in 2017. RESULTS: Hot topics include screening for osteoporosis, novel anabolic drugs such as romosozumab and abaloparatide for osteoporosis and rare metabolic bone diseases, as well as long-term efficacy of denosumab and possible risk of multiple vertebral fractures following its discontinuation. Other selected articles cover effectiveness of bisphosphonates and changes in mineralization after long-term use, new guidelines for glucocorticoid- and aromatase inhibitor-induced osteoporosis, increasing use of high-dose vitamin D supplements despite lack of evidence for their widespread high-dose use, and cardiovascular safety concerns surrounding the use of calcium supplements. Other topics discussed are effects of diabetes on bone health, reciprocal crosstalk between bone cells and adipose tissue, and resistance exercise training to prevent bone loss and sarcopenia. CONCLUSIONS: These papers offer a hopeful outlook for a better treatment and management of patients with osteoporosis and other metabolic bone diseases anno 2018.

A shortened tamoxifen induction scheme to induce CreER recombinase without side effects on the male mouse skeleton.

The selective estrogen receptor modulator tamoxifen exerts estrogen agonistic or antagonistic actions on several tissues, including bone. The off-target effects of tamoxifen are one of the most widely recognized pitfalls of tamoxifen-inducible Cre recombinases (CreERs), potentially confounding the phenotypic findings. Still, the validation of tamoxifen induction schemes that minimize the side effects of the drug has not been addressed. Here, we compared the side effects on the skeleton and other androgen-responsive targets of a shortened tamoxifen regimen (2 doses of 190 mg/kg body weight by oral gavage) to a standard protocol (4 doses) and determined their efficiency in inducing CreER-mediated gene deletion. In addition, both a vehicle- and a 10-dose group, which served as a positive control for tamoxifen side effects, were also included. For this purpose, we generated male mice with a floxed androgen receptor (AR) and a neuron-specifically expressed CreER. Treatment with two doses of tamoxifen was the only regimen that did not diminish androgenic bioactivity, as assessed by both seminal vesicles and levator ani/bulbocavernosus muscle weights and serum testosterone concentrations. Similarly, trabecular and cortical femoral bone structure were dramatically altered by both the standard and high-dose protocols but not by the shortened version. Serum osteocalcin and bone-gene expression analyses confirmed the absence of effects on bone by 2 doses of tamoxifen. This protocol decreased AR mRNA levels efficiently and specifically in the nervous system. Thus, we optimized a protocol for tamoxifen-induced CreER gene deletion in mice without off-target effects on bone and male reproductive organs.