ECE2014 Poster Presentations Bone and Osteoporosis (36 abstracts)
Factors associated with vertebral fractures in patients with primary hyperparathyroidism
Cristina Eller-Vainicher 1 , Claudia Battista 2 , Vito Guarneri 2 , Serena Palmieri 1 , Antonio S Salcuni 2 , Giuseppe Guglielmi 3 , Sabrina Corbetta 4 , Salvatore Minisola 5 , Anna Maria Spada 1 , Geoffrey N Hendy 6 , David E C Cole 7 , Iacopo Chiodini 1 & Alfredo Scillitani 2
1Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; 2Unit of Endocrinology ‘Casa Sollievo della Sofferenza’, IRCCS, San Giovanni Rotondo, Foggia, Italy; 3Unit of Radiology ‘Casa Sollievo della Sofferenza’, IRCCS, San Giovanni Rotondo, Foggia, Italy; 4Department of Biomedical Sciences for Health, University of Milan, Unit of Endocrinology and Diabetology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy; 5Department of Internal Medicine and Medical Disciplines, ’Sapienza’ Rome University, Rome, Italy; 6Departments of Medicine, Physiology, and Human Genetics, McGill University, Montreal, Canada; 7Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Introduction: Risk of vertebral fracture (VFx) is in part independent of bone mineral density (BMD) in primary hyperparathyroidism (PHPT). The aim of this study was to examine whether other factors, including the genotype of common polymorphisms in the calcium-sensing receptor (CASR) gene, are associated with VFx.
Patients and methods: In 266 Caucasian PHPT patients, serum calcium, phosphate, creatinine, total alkaline phosphatase, intact PTH, 25-hydroxyvitamin D and 24 h urine calcium were measured. BMD was measured by dual-energy X-ray absorptiometry (DXA) and expressed as Z-score at spine (Z-LS) and femoral neck (Z-FN). Morphometric VFx was identified by spinal radiograph and CASR A986S and R990G genotypes assessed by PCR amplification and sequencing of genomic DNA.
Results: PHPT patients with VFx (n=100, 37.6%) had lower serum calcium levels (10.8±0.7 mg/dl) and Z-LS BMD (−1.0±1.44), higher age (61±10.1 years) and prevalence (51%) of one or two S alleles of the CASR A986S single nucleotide polymorphism (SNP), than those without VFx (11.2±1.0 mg/dl, −0.57±0.97, 57.9±13.1 years and 38% respectively, P<0.05% for all comparisons). VFx was associated with increased age (OR 1.04, 95% CI 1.01–1.17, P=0.017), decreased serum calcium levels (OR 1.49, 95% CI 0.99–2.32, P=0.05) and Z-LS BMD (OR 1.8, 95% CI 1.32–2.5, P<0.0001) and presence of one or two S alleles of the CASR A986S SNP (OR=2.27, 95% CI 1.14–4.54, P=0.02), regardless of confounders. The cut-offs for age, serum calcium and Z-LS BMD that best predict VFx were 58 years, 10.8 mg/dl, and −1.0 respectively. Sensitivity (92%) and specificity (92.8%) for predicting VFx were maximal in the presence or absence of all three factors. The presence of ≥2 factors plus one or two S alleles of the CASR A986S SNP was associated with VFx (OR 4.71, 95% CI 2.19–10.12, P<0.0001), regardless of confounders.
Conclusions: In PHPT asymptomatic VFx is associated positively with age, negatively with serum calcium and spinal BMD, and with the CASR A986S SNP, while the R990G SNP, that has been previously associated with kidney stones in PHPT is not involved in VFx risk.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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