{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:45:02Z","timestamp":1790549102878,"version":"4.1.0"},"reference-count":38,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Context: 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-\u03baB ligand and osteoprotegerin (OPG) in primary hyperparathyroidism and their relationship to bone loss.<\/jats:p>\n               <jats:p>Patients and Methods: Twenty-nine patients with primary hyperparathyroidism had baseline circulating soluble receptor activator of nuclear factor-\u03baB ligand (sRANKL) and OPG measured. The relationship to biochemical markers of bone turnover and changes in bone mineral density over 2 yr was examined.<\/jats:p>\n               <jats:p>Results: Baseline sRANKL levels were elevated (1.7 \u00b1 0.1 pmol\/liter), whereas OPG remained in the normal range (5.6 \u00b1 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 &amp;lt; 0.01; serum N-telopeptide of type I collagen: r = 0.37, P &amp;lt; 0.05). Furthermore, sRANKL correlated with both IL-6 and IL-6 soluble receptor (IL-6sR) (r = 0.47, P &amp;lt; 0.05 and r = 0.55, P &amp;lt; 0.005, respectively). Serum sRANKL levels also correlated with bone loss at the total femur (r = \u22120.53, P &amp;lt; 0.01). Lastly, a high value of sRANKL in combination with values of IL-6 and IL-6sR in the upper quartile (sRANKL \u2265 1.81 pg\/ml, IL \u22126 \u2265 11.8 pg\/ml, and IL-6sR \u2265 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 (\u22122.7 \u00b1 1.7% vs. +0.5 \u00b1 0.3%; n = 4 vs. n = 19, P &amp;lt; 0.05).<\/jats:p>\n               <jats:p>Conclusion: 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.<\/jats:p>","DOI":"10.1210\/jc.2007-1645","type":"journal-article","created":{"date-parts":[[2007,12,12]],"date-time":"2007-12-12T04:47:23Z","timestamp":1197434843000},"page":"967-973","source":"Crossref","is-referenced-by-count":39,"title":["The Role of the Receptor Activator of Nuclear Factor-\u03baB Ligand\/Osteoprotegerin Cytokine System in Primary Hyperparathyroidism"],"prefix":"10.1210","volume":"93","author":[{"given":"Inaam A.","family":"Nakchbandi","sequence":"first","affiliation":[{"name":"University of Heidelberg (I.A.N.), 69120 Heidelberg, Germany"},{"name":"Department of Max-Planck Institute for Biochemistry (I.A.N.), 69120 Heidelberg, Germany"},{"name":"Section of Endocrinology (I.A.N., K.L.I.), Yale University School of Medicine, New Haven, Connecticut 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Osteoporosis Center (R.L.), Hamden, Connecticut 06518"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kinder","sequence":"additional","affiliation":[{"name":"Department of Medicine, and Department of Surgery (B.K.), Yale University School of Medicine, New Haven, Connecticut 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl L.","family":"Insogna","sequence":"additional","affiliation":[{"name":"Section of Endocrinology (I.A.N., K.L.I.), Yale University School of Medicine, New Haven, Connecticut 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071616133725500_R1","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1056\/NEJM199910213411701","article-title":"A 10-year prospective study of primary hyperparathyroidism 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interleukin-6.","volume":"90","author":"Tamura","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071616133725500_R5","doi-asserted-by":"crossref","first-page":"4946","DOI":"10.1210\/jc.2001-011814","article-title":"Circulating levels of interleukin-6 soluble receptor predict rates of bone loss in patients with primary hyperparathyroidism.","volume":"87","author":"Nakchbandi","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616133725500_R6","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1210\/endo.140.10.7036","article-title":"A role for interleukin-6 in parathyroid hormone-induced bone resorption in vivo.","volume":"140","author":"Grey","year":"1999","journal-title":"Endocrinology"},{"key":"2020071616133725500_R7","doi-asserted-by":"crossref","first-page":"E784","DOI":"10.1152\/ajpendo.00029.2005","article-title":"IL-6 is not required for parathyroid hormone stimulation of RANKL expression, osteoclast formation, and bone loss in 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function.","volume":"141","author":"Udagawa","year":"2000","journal-title":"Endocrinology"},{"key":"2020071616133725500_R11","first-page":"1111","article-title":"Osteoblasts are not the source of RANKL and OPG in bone but are required for maintenance of osteoclast function","volume":"21","author":"O\u2019Brien","year":"2006","journal-title":"J Bone Miner Res"},{"key":"2020071616133725500_R12","doi-asserted-by":"crossref","first-page":"3332","DOI":"10.1210\/jc.2003-032066","article-title":"Changes in serum receptor activator of nuclear factor-\u03baB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1\u201334).","volume":"89","author":"Buxton","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616133725500_R13","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1172\/JCI10483","article-title":"Chronic alcohol ingestion induces osteoclastogenesis and bone loss through 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