osteoprotegerin and Hyperparathyroidism--Primary

Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women. Th17 lymphocytes and the released cytokine IL-17A play an important role in bone metabolism. Th17 cells have been shown to be activated by PTH, and peripheral blood T cells from patients affected with PHPT express higher levels of IL-17A mRNA than controls.. To investigate circulating levels of IL-17A and the ratio RANKL/OPG, as markers of osteoclastogenesis, in 50 postmenopausal PHPT women compared with postmenopausal osteoporotic non-PHPT women (. In postmenopausal PHPT women, circulating IL-17A levels were similar to those detected in postmenopausal non-PHPT women, showing a disruption of the relationship observed in postmenopausal osteoporosis among circulating PTH, sRANKL, OPG, IL-17A, and bone demineralization in postmenopausal PHPT women. The data support an osteogenic effect of IL-17A in postmenopausal PHPT women.

Topics: Aged; Calcium; Female; Humans; Hyperparathyroidism, Primary; Interleukin-17; Middle Aged; Osteoprotegerin; Postmenopause; Receptor Activator of Nuclear Factor-kappa B

Surgical treatment for primary hyperparathyroidism (PHPT) improves bone metabolism. Osteocalcin (OC) and its undercarboxylated form (ucOC) are associated with bone and energy metabolism. Osteopontin (OPN), a multifunctional protein expressed in bone, is involved in resorption, along with β-carboxyl-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and osteoprotegerin (OPG). Our aim was to investigate these biomarkers of bone metabolism in patients with PHPT.. We examined 30 individuals with PHPT, in a clinical research facility, before and 1 month following parathyroidectomy. Circulating levels of OC, ucOC, OPN, β-CTX, and OPG were examined as bone biomarkers along with inflammatory markers (e.g., interleukin-6 [IL-6], lipocalin-2), insulin resistance (i.e., homeostasis model assessment for insulin resistance [HOMA-IR]), adiposity (i.e., leptin, adiponectin), PTH, calcium, 25-hydroxyvitamin D, creatinine, and demographics.. The lower 1-month postoperative OPN and ucOC levels in PHPT seem to indicate reduced bone resorption. Decreased ucOC levels may also suggest lower energy demands postoperatively.

Topics: Adiponectin; Aged; Female; Follow-Up Studies; Humans; Hyperparathyroidism, Primary; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Parathyroidectomy

Topics: Alendronate; Bone Density Conservation Agents; Bone Remodeling; Female; Humans; Hyperparathyroidism, Primary; Male; Osteoprotegerin; RANK Ligand

Topics: Alendronate; Bone Density Conservation Agents; Bone Remodeling; Female; Humans; Hyperparathyroidism, Primary; Male; Osteoprotegerin; RANK Ligand

Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and its decoy receptor osteoprotegerin (OPG) play key roles in regulating bone turnover. The OPG/RANKL/RANK system is regulated by many hormones and cytokines, among which parathormone (PTH) seems to be one of the most important. Primary hyperparathyroidism (PHPT) with chronic excess of PTH and enhanced bone resorption provides an opportunity to observe the relationships between PTH, OPG and RANKL. From a group of 63 patients with PHPT, 29 underwent effective parathyroidectomy (PTX) and 33 were treated with alendronate. After one year, bone mineral density (BMD) improved in both groups, but the biochemical disturbances and PTH returned to normal only after PTX. The baseline serum concentrations of OPG and RANKL were higher in PHPT patients than in healthy controls, whilst the OPG/RANKL-F ratio was lower. The mean OPG concentration did not change after PTX, and slightly increased after alendronate treatment despite the unchanged PTH. Twelve months after treatment, RANKL slightly declined in both groups and the ratio of OPG/RANKL consistently increased. Serum OPG and RANKL did not correlate with PTH before or after PTX or alendronate treatment. In conclusion, bone resorption in PHPT is accompanied by a high serum concentration of OPG and RANKL as well as a low OPG/RANKL ratio. Both parathyroidectomy and treatment with alendronate diminish bone resorption, and correct the OPG/RANKL ratio in favor of OPG, although the mechanisms of their actions are different. Serum OPG concentration does not depend directly on PTH.

Topics: Adult; Alendronate; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Case-Control Studies; Female; Humans; Hyperparathyroidism, Primary; Male; Osteoprotegerin; Parathyroidectomy; RANK Ligand

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.

Topics: Adult; Aged; Alleles; Bone Density; Cross-Sectional Studies; Female; Fractures, Bone; Genotype; Homozygote; Humans; Hyperparathyroidism, Primary; Lithiasis; Male; Middle Aged; Odds Ratio; Osteoprotegerin; Parathyroid Hormone; Polymorphism, Single Nucleotide; RANK Ligand

The mechanisms of action of PTH on bone in vivo remain incompletely understood. The objective of this investigation was to examine changes in serum levels of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin (OPG) in primary hyperparathyroidism and their relationship to bone loss.. Twenty-nine patients with primary hyperparathyroidism had baseline circulating soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) and OPG measured. The relationship to biochemical markers of bone turnover and changes in bone mineral density over 2 yr was examined.. Baseline sRANKL levels were elevated (1.7+/-0.1 pmol/liter), whereas OPG remained in the normal range (5.6+/-0.4 pmol/liter). Circulating sRANKL did not correlate with PTH but did correlate with markers of bone resorption (urine deoxypyridinoline cross-links: r=0.51, P<0.01; serum N-telopeptide of type I collagen: r=0.37, P<0.05). Furthermore, sRANKL correlated with both IL-6 and IL-6 soluble receptor (IL-6sR) (r=0.47, P<0.05 and r=0.55, P<0.005, respectively). Serum sRANKL levels also correlated with bone loss at the total femur (r=-0.53, P<0.01). Lastly, a high value of sRANKL in combination with values of IL-6 and IL-6sR in the upper quartile (sRANKL>or=1.81 pg/ml, IL -6>or=11.8 pg/ml, and IL-6sR>or=45.6 ng/ml) defined a group of four women with significantly greater rates of bone loss at the total femur than the remaining patients (-2.7+/-1.7% vs. +0.5+/-0.3%; n=4 vs. n=19, P<0.05).. Determination of circulating levels of sRANKL may be useful in identifying patients with mild primary hyperparathyroidism at greater risk for bone loss. The fact that circulating sRANKL did not correlate with PTH but did correlate with markers of bone resorption suggests that skeletal responsiveness to PTH may differ in this disease.

Topics: Aged; Bone Density; Bone Remodeling; Female; Humans; Hyperparathyroidism, Primary; Interleukin-6; Male; Middle Aged; Osteoprotegerin; Parathyroid Hormone; RANK Ligand; Receptors, Interleukin-6