HIGH RISK OF PARATHYROID CARCINOMA AND GENETIC SCREENING IN THE FIRST DIAGNOSED ROMANIAN FAMILY WITH HYPERPARATHYROIDISM-JAW TUMOR SYNDROME AND A GERMLINE MUTATION OF THE CDC73 GENE.

CONTEXT: Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene. OBJECTIVE: To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene. SUBJECTS AND METHODS: Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed. RESULTS: Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism. CONCLUSIONS: We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.

INCIDENCE AND TIME TREND OF HIP FRACTURES IN ROMANIA: A NATIONWIDE STUDY FROM 2008 TO 2018.

BACKGROUND: Hip fractures are a major issue of public health as they are responsible for high morbidity, excess mortality and costs. There are differences in Europe and worldwide in the incidence rates of hip fractures and time trends, in the context of the population aging. Ten years ago, we characterized the incidence of hip fracture in Romania using data from the national hospital discharge register. OBJECTIVE: This is the first Romanian study to assess the hip fracture incidence rates over a period of 11 years, between 2008 and 2018. SUBJECTS AND METHODS: This analysis is a nationwide retrospective study on hospitals reporting primary DRG data on hip fracture, using a rigorous definition with both diagnostic and surgical procedure codes. The population aged 40+ was stratified in 5-year intervals and both the crude incidence rates and the adjusted incidence rates of hip fracture using standardization on age for the 2018 reference population were calculated in women and men. RESULTS: From 2008 to 2018, the number of hip fractures rose by 53 % in women (from 7513 to 11512) and 22.4 % in men (from 4266 to 5220). Meanwhile, the Romanian population over 40 years increased by 12.5% in women and 14.2% in men. The crude incidence rate rose by 36.2% in women and 7.2% in men and the age-standardized incidence rates by 27.4% in women and 6% in men. These increases are mostly based on 85+ age populations' changes. CONCLUSIONS: In Romania, the hip fractures incidence continues to grow throughout an 11-year-period, especially in women, representing an increasing burden for our society.

TRABECULAR BONE SCORE (TBS) HAS A POOR DISCRIMINATIVE POWER FOR VERTEBRAL FRACTURES IN 153 ROMANIAN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM.

CONTEXT: Trabecular Bone Score (TBS) has been recently proposed as a good tool to investigate secondary osteoporosis. OBJECTIVE: The aim of this study was to assess TBS from spine DXA images in patients with primary hyperparathyroidism (PHPT) and look at its correlates. SUBJECTS AND METHODS: 153 patients, mean age 59.1 ± 12.1 yrs, females and males (10%), mean BMI 26.2 ± 4.8 kg/m2, mean serum calcium and PTH of 11.3 ± 1.2 mg/dL and 232 ± 329 pg/mL, respectively; 89% had osteoporosis/osteopenia by LS DXA and 46% had renal involvement. There were 7.6% patients with vertebral fractures, 13.2% patients with nonvertebral fractures. TBS indices were derived from LS-DXA images and cutoff points used were those previously reported. RESULTS: Mean TBS was in the partially degraded range (1.258 ± 0.115); 32% of patients had degraded microarchitecture (TBS ≤ 1.20), 51% had partially degraded microarchitecture (TBS > 1.20 and < 1.35) and 17% had normal TBS. TBS was significantly correlated with areal BMD both at the LS (r=0.544; p<0.001) and FN (r = 0.315; p < 0.001), and negatively with age (r= - 0.354; p < 0.001) and years since menopause - YSM (r = - 0.257, p = 0.005). Patients with vertebral fractures had mean values of TBS in the degraded range, significantly lower than those without vertebral fractures (1.173 ± 0.076 vs. 1.263 ± 0.115; p = 0.006). The presence of vertebral fracture was independently associated only with YSM (OR = 1.131, 95% CI = 0.032 - 0.214, p = 0.008) but not with TBS. CONCLUSIONS: In a cohort of symptomatic PHPT patients, including postmenopausal, premenopausal and male patients, we have shown that TBS was in the partially degraded range, but it was not independently associated with fractures.

SUSPECTED NON-LRP5 MUTATION ASSOCIATED WITH HIGH BONE MASS UNALTERED BY CONCURRENT SYMPTOMATIC PRIMARY HYPERPARATHYROIDISM OF LONG DURATION.

BACKGROUND: Unexplained high bone mass (HBM) (Bone Mineral Density-BMD Z-score at the lumbar spine or hip of ≥+3.2 SD, or a combined spine and hip Z score ≥4 SD) after routine bone densitometry occurs with a prevalence of approximately 2 out of 1.000 and is currently believed to be a mild form of skeletal dysplasia (1). RESULTS: We present the case of a patient with unexplained HBM (Z-scores at L3, L1-L4, total hip and radius total were +3, +2.7, +2 and +1.8, respectively) and concurrent symptomatic primay hyperparathyroidism (total serum calcium 11.9 mg/dL, serum Parathyroid Hormone - PTH 189.3 pg/mL) of long duration. There were no significant BMD changes at any skeletal site after the surgical cure of hyperparathyroidism. Testing for LRP (low density lipoprotein receptor-related proteins) 5 gene mutations was negative. CONCLUSIONS: We presented an unusual case of the association of a HBM with primary hyperparathyroidism with resistance to the catabolic action of PTH. In spite of the negative result of LRP5 testing we do believe that a mutation of a gene involved in the Wnt pathway in bone is responsible.