"Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density".
ABSTRACT Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κβ (OPG/RANKL) system. Several studies have confirmed that OPG (osteoprotegerin) and RANKL (ligand of the receptor activator of nuclear factor-κβ) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the OPG and the rs2277438 SNP of the RANKL, in patients with sporadic PHPT.
We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied.
Regarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the OPG rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the RANKL in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA).
Our study provides the first evaluation of the relationship between SNPs of the OPG/RANK system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.
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ABSTRACT: Most patients with primary hyperparathyroidism in the 1980s do not have evidence of bone disease when they are evaluated by conventional radiography. We sought to determine whether skeletal involvement can be appreciated when more sensitive techniques, such as bone densitometry and bone biopsy, are utilized. We investigated 52 patients with primary hyperparathyroidism. They had mild hypercalcemia, 2.8 +/- 0.03 mmol/liter (11.1 +/- 0.1 mg/dl), low normal phosphorus, 0.9 +/- 0.03 mmol/liter (2.8 +/- 0.1 mg/dl), and no symptoms or specific radiological signs of skeletal involvement. The greatest reduction in bone mineral density was found at the site of predominantly cortical bone, the radius (0.54 +/- 0.1 g/cm; 79 +/- 2% of expected), whereas the site of predominantly cancellous bone, the lumbar spine (1.07 +/- 0.03 g/cm2), was normal (95 +/- 3% of expected). The site of mixed composition, the femoral neck (0.78 +/- 0.14 g/cm2), gave an intermediate value (89 +/- 2% of expected). Preferential involvement of cortical bone with apparent preservation of cancellous bone in primary hyperparathyroidism was confirmed by percutaneous bone biopsy. Over 80% of patients had a mean cortical width below the expected mean, whereas cancellous bone volume in over 80% of patients was above the expected mean. The results indicate that the majority of patients with asymptomatic primary hyperparathyroidism have evidence by bone densitometry and bone biopsy for cortical bone disease. The results also indicate that the mild hyperparathyroid state may be protective of cancellous bone. The therapeutic implications of these observations await further longitudinal experience with this study population.Journal of Bone and Mineral Research 07/1989; 4(3):283-91. · 6.13 Impact Factor
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ABSTRACT: Several studies have demonstrated that cancellous bone mass and architecture are preserved in postmenopausal women with primary hyperparathyroidism (PHPT). To investigate the mechanism(s) that could account for this observation, we analyzed features of bone formation in 19 postmenopausal women with PHPT by bone histomorphometry. The results were compared with those from a comparable group of 34 healthy, postmenopausal women. Patients with PHPT were similar to control subjects in cancellous bone area as well as in trabecular width, separation, and number. However, in PHPT, elevations were observed in indexes of bone turnover, such as eroded surface, osteoid surface, mineralizing surface, bone formation rate at the tissue level, and activation frequency. At the level of the bone-remodeling unit, women with PHPT had significantly higher values for the wall width of trabecular bone packets (40.26 +/- 0.36 vs. 34.58 +/- 0.45 mm), the adjusted apposition rate (0.40 +/- 0.04 vs. 0.29 +/- 0.03 mm/day), and the active formation period (67.8 +/- 5.1 vs. 57.3 +/- 2.3 days). These findings are consistent with a stimulatory action of elevated PTH levels on the duration of the active bone formation phase in individual remodeling units and may account at least in part for the preservation of cancellous bone in postmenopausal women with mild PHPT.Journal of Clinical Endocrinology & Metabolism 06/1999; 84(5):1562-6. · 6.43 Impact Factor
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ABSTRACT: The clinical presentation of primary hyperparathyroidism (pHPT) has changed during the last half century, and the diagnosis is now more often made by chance in patients with no specific symptoms. The present study is a randomized, controlled trial that investigates the effects of parathyroidectomy or medical observation in mild asymptomatic pHPT on morbidity and quality of life (QoL). A total of 191 patients (26 men) with asymptomatic pHPT [mean age 64.2 +/- 7.4 (sd) yr] were recruited in the study and randomized to medical observation (serum calcium level 2.69 +/- 0.08 mmol/liter) or surgery (2.70 +/- 0.08 mmol/liter). We here report baseline and 1 (n = 119) and 2 yr data (n = 99) on those who had completed the follow-up visits by the end of the inclusion period. At baseline, the patients had significantly lower QoL (SF-36) and more psychological symptoms, compared with age- and sex-matched healthy subjects. The two groups were similar at baseline, and no clinically significant changes in these parameters were seen during the observation time. Calcium and PTH normalized after surgery. The areal bone mineral density increased in the group randomized to operation, whereas the bone mineral density remained stable in the medical observation group. No change in kidney function (creatinine) or blood pressure was observed longitudinally or between the groups. Asymptomatic patients with mild pHPT have decreased QoL and more psychological symptoms than normal controls. No benefit of operative treatment, compared with medical observation, was found on these measures so far.Journal of Clinical Endocrinology & Metabolism 06/2007; 92(5):1687-92. · 6.43 Impact Factor