Abstract
The effect of parathyroid hormone (PTH) on the production of osteoprotegerin (OPG) remains controversial. Most in vitro studies indicate that PTH decreases OPG secretion by the osteoblast, but in vivo observations are conflicting. In primary hyperparathyroidism (PHPT), hypersecretion of PTH leads to enhanced bone resorption and formation with increased risk of fracture. Patients with PHPT are cured by surgery, resulting in normalization of PTH levels and bone metabolism, but the concomitant effects on OPG production are not known. The hypothesis of the present study was that the circulating level of OPG is diminished in patients with PHPT and increases with successful parathyroidectomy. We also speculated that serum OPG may determine the magnitude of bone loss up to the time of surgery. In the present study, 20 patients (17 women and 3 men, mean age 62 y) with PHPT who were candidates for surgical cure were examined before and 12 months after surgery. Bone turnover markers decreased and BMD increased significantly after surgery. Serum OPG did not correlate with PTH before surgery (r = 0.07, P = 0.77) and was not affected by parathyroidectomy (P = 0.79). After normalization of PTH, bone formation markers showed significant (P1NP) and near-significant (osteocalcin) correlations with serum OPG. In conclusion, serum OPG is not decreased in patients with PHPT, nor is serum OPG to any demonstrable extent regulated by PTH pre- or postoperatively.
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References
EA O’Brien JH Williams MJ Marshall (2000) ArticleTitleOsteoprotegerin ligand regulates osteoclast adherence to the bone surface in mouse calvaria. Biochem Biophys Res Commun 274 281–290 Occurrence Handle10.1006/bbrc.2000.3129 Occurrence Handle1:CAS:528:DC%2BD3cXltVOks7k%3D Occurrence Handle10913332
DL Lacey E Timms HL Tan MJ Kelley CR Dunstan T Burgess et al. (1998) ArticleTitleOsteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93 165–176 Occurrence Handle9568710
E Jimi S Akiyama T Tsurukai et al. (1999) ArticleTitleOsteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function. J Immunol 163 434–442 Occurrence Handle1:CAS:528:DyaK1MXkt1ShsL8%3D Occurrence Handle10384146
H Hsu DL Lacey CR Dunstan et al. (1999) ArticleTitleTumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA 96 3540–3545 Occurrence Handle1:CAS:528:DyaK1MXjslCitL8%3D Occurrence Handle10097072
H Yasuda N Shima N Nakagawa et al. (1998) ArticleTitleOsteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95 3597–3602 Occurrence Handle1:CAS:528:DyaK1cXitlKjsLY%3D Occurrence Handle9520411
WS Simonet DL Lacey CR Dunstan et al. (1997) ArticleTitleOsteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89 309–319 Occurrence Handle9108485
H Yasuda N Shima N Nakagawa et al. (1998) ArticleTitleIdentity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139 1329–1337 Occurrence Handle9492069
NO Vidal H Brandstrom KB Jonsson C Ohlsson (1998) ArticleTitleOsteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids. J Endocrinol 159 191–195 Occurrence Handle1:CAS:528:DyaK1cXmsFOnurs%3D Occurrence Handle9795357
JE Onyia RR Miles X Yang et al. (2000) ArticleTitleIn vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene. J Bone Miner Res 15 863–871 Occurrence Handle1:CAS:528:DC%2BD3cXjt1Crs70%3D Occurrence Handle10804015
K Itoh N Udagawa K Matsuzaki et al. (2000) ArticleTitleImportance of membrane- or matrix-associated forms of M-CSF and RANKL/ODF in osteoclastogenesis supported by SaOS-4/3 cells expressing recombinant PTH/PTHrP receptors. J Bone Miner Res 15 1766–1775
SK Lee JA Lorenzo (1999) ArticleTitleParathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140 3552–3561 Occurrence Handle1:CAS:528:DyaK1MXkslKru74%3D Occurrence Handle10433211
P Szulc LC Hofbauer AE Heufelder S Roth PD Delmas (2001) ArticleTitleOsteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone status. J Clin Endocrinol Metab 86 3162–3165
U Fraher PH Watson M Kisiel BV Natale AB Hodsman (2000) Measurement of circulating osteoprotegerin (OPG) in human sera: inhibition of circulating OPG in osteoporotic patients treated with hPTH (1-34) (abstract). ASBMR 2000 Toronto
WS Browner LY Lui SR Cummings (2001) ArticleTitleAssociations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 86 631–637 Occurrence Handle1:CAS:528:DC%2BD3MXht1Knsbc%3D Occurrence Handle11158021
P Christiansen T Steiniche K Brixen et al. (1997) ArticleTitlePrimary hyperparathyroidism: biochemical markers and bone mineral density at multiple skeletal sites in Danish patients. Bone 21 93–99 Occurrence Handle10.1016/S8756-3282(97)00078-1 Occurrence Handle1:CAS:528:DyaK2sXkslamsbg%3D Occurrence Handle9213014
P Vestergaard CL Mollerup VG Frokjaer et al. (2000) ArticleTitleCohort study of risk of fracture before and after surgery for primary hyperparathyroidism. BMJ 321 598–602 Occurrence Handle10.1136/bmj.321.7261.598 Occurrence Handle1:STN:280:DC%2BD3cvmvF2lsw%3D%3D Occurrence Handle10977834
P Christiansen T Steiniche K Brixen et al. (1999) ArticleTitlePrimary hyperparathyroidism: effect of parathyroidectomy on regional bone mineral density in Danish patients: a three-year follow-up study. Bone 25 589–595 Occurrence Handle10.1016/S8756-3282(99)00207-0 Occurrence Handle1:STN:280:DC%2BD3c%2FjvFOgtQ%3D%3D Occurrence Handle10574580
B Abrahamsen TB Hansen LB Jensen AP Hermann P Eiken (1997) ArticleTitleSite of osteodensitometry in perimenopausal women: correlation and limits of agreement between anatomic regions. J Bone Miner Res 12 1471–1479
NJ Horwood J Elliott TJ Martin MT Gillespie (1998) ArticleTitleOsteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 139 4743–4746 Occurrence Handle1:CAS:528:DyaK1cXntFWlurw%3D Occurrence Handle9794488
DS Rao M Honasoge GW Divine et al. (2000) ArticleTitleEffect of vitamin D nutrition on parathyroid adenoma weight: pathogenetic and clinical implications. J Clin Endocrinol Metab J . 1054–1058
P Christiansen (2001) ArticleTitleThe skeleton in primary hyperparathyroidism: a review focusing on bone remodeling, structure, mass, and fracture. APMIS (suppl) 102 1–52
T Steiniche P Christiansen A Vesterby et al. (2000) ArticleTitlePrimary hyperparathyroidism: bone structure, balance, and remodeling before and 3 years after surgical treatment. Bone 26 535–543 Occurrence Handle10.1016/S8756-3282(00)00260-X Occurrence Handle10773596
T Uzawa M Hori S Ejiri H Ozawa (1995) ArticleTitleComparison of the effects of intermittent and continuous administration of human parathyroid hormone(1-34) on rat bone. Bone 16 477–484 Occurrence Handle1:CAS:528:DyaK2MXlvVehs78%3D Occurrence Handle7605709
R Podbesek C Edouard PJ Meunier et al. (1983) ArticleTitleEffects of two treatment regimes with synthetic human parathyroid hormone fragment on bone formation and the tissue balance of trabecular bone in greyhounds. Endocrinology 112 1000–1006 Occurrence Handle1:CAS:528:DyaL3sXht1Sitr0%3D Occurrence Handle6822201
CS Tam JN Heersche TM Murray JA Parsons (1982) ArticleTitleParathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. Endocrinology 110 506–512 Occurrence Handle1:CAS:528:DyaL38XhtlKnu70%3D Occurrence Handle7056211
S Khosla HM Arrighi LJ Melton et al. (2002) ArticleTitleCorrelates of osteoprotegerin levels in women and men. Osteoporos Int 13 394–399 Occurrence Handle10.1007/s001980200045
K Yano E Tsuda N Washida et al. (1999) ArticleTitleImmunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14 518–527 Occurrence Handle1:STN:280:DyaK1M3ltVygsw%3D%3D Occurrence Handle10234572
PJ Bekker D Holloway A Nakanishi et al. (2001) ArticleTitleThe effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res 16 348–360 Occurrence Handle1:CAS:528:DC%2BD3MXptlOquw%3D%3D Occurrence Handle11204435
E Tsuda M Goto S Mochizuki et al. (1997) ArticleTitleIsolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun 234 137–142 Occurrence Handle10.1006/bbrc.1997.6603 Occurrence Handle1:CAS:528:DyaK2sXjt1ynsLw%3D Occurrence Handle9168977
TJ Yun PM Chaudhary GL Shu et al. (1998) ArticleTitleOPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol 161 6113–6121 Occurrence Handle1:CAS:528:DyaK1cXnslCrt7w%3D Occurrence Handle9834095
Acknowledgements
The authors are grateful to consultant endocrinologist, Kim Brixen for valuable comments and discussion. We would also like to thank technicians A. Riis Madsen, B. Aarup Kristensen, K. R. Westermann and E. Rettmer, This work was supported by research grants from The Novo Nordic Foundation, Aage Louis-Hansens Mindefond, Institute of Clinical Research Odense University Hospital and Eli Lilly’s osteoporosis foundation.
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Stilgren, L., Hegedüs, L., Beck-Nielsen, H. et al. Osteoprotegerin Levels in Primary Hyperparathyroidism: Effect of Parathyroidectomy and Association with Bone Metabolism . Calcif Tissue Int 73, 210–216 (2003). https://doi.org/10.1007/s00223-002-2100-8
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DOI: https://doi.org/10.1007/s00223-002-2100-8