Osteocalcin and its forms across the lifespan in adult men

Smith, Cassandra<sup>1,2</sup>; Voisin, Sarah<sup>1</sup>; Al Saedi, Ahmed<sup>2,3</sup>; Phu, Steven<sup>2,3</sup>; Brennan-Speranza, Tara<sup>4</sup>; Parker, Lewan<sup>5</sup>; Eynon, Nir<sup>1,6</sup>; Hiam, Danielle<sup>1</sup>; Yan, Xu<sup>1</sup>; Scott, David<sup>2,7</sup>; Blekkenhorst, Lauren C.<sup>8,9</sup>; Lewis, Joshua R.<sup>8,9,10</sup>; Seeman, Ego<sup>11</sup>; Byrnes, Elizabeth<sup>12</sup>; Flicker, Leon<sup>9,13</sup>; Duque, Gustavo<sup>2,3</sup>; Yeap, Bu B.<sup>9,14</sup>; Levinger, Itamar<sup>1,2,3</sup>

Affiliations

¹Institute for Health and Sport (iHeS), Victoria University, Melbourne, VIC, Australia

²Australian Institute for Musculoskeletal Science (AIMSS), University of Melbourne and Western Health, St Albans, VIC, Australia

³Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia

⁴Department of Physiology and Bosch Institute for Medical Research, University of Sydney, New South Wales, Australia

⁵Institute for Physical Activity and Nutrition (IPAN), Deakin University, Geelong, VIC, Australia

⁶Murdoch Childrens Research Institute, Melbourne, Australia

⁷School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia

⁸School of Medical and Health Sciences, Edith Cowan University, Perth, Australia

⁹Medical School, University of Western Australia, Perth, Australia

¹⁰Centre for Kidney Research, Children's Hospital at Westmead School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia

¹¹University of Melbourne and the Department of Endocrinology, Austin Health and the Mary Mackillop Institute of Healthy Aging, Australian Catholic University, Melbourne, Australia

¹²Department of Biochemistry, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Australia

¹³Western Australian Centre for Health & Ageing, University of Western Australia, Perth, Australia

¹⁴Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia

Abstract and keywords

Purpose: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease.

Methods: Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis.

Results: The normal ranges for young men (≤30 years) were: tOC 17.9–56.8 ng/mL, ucOC 7.1–22.0 ng/mL, cOC 8.51–40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a “U” shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ∼31%, while body mass index explained ∼4%, of the variance in the ratios.

Conclusions: We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.

Keywords: Osteocalcin; Aging; Reference ranges; Bone; Bone turnover

Links

DOI: 10.1016/j.bone.2019.115085

PubMed: 31622778

WoS: 000503321100010

History

Received: 2019-06-21

Revised: 2019-09-26

Accepted: 2019-09-27

Online: 2019-10-14

Cited Works (5)

Year	Entry
2019	Parker L, Lin X, Garnham A, McConell G, Stepto NK, Hare DL, Byrnes E, Ebeling PR, Seeman E, Brennan‐Speranza TC, Levinger I. Glucocorticoid‐induced insulin resistance in men is associated with suppressed undercarboxylated osteocalcin. J Bone Miner Res. January 2019;34(1):49-58.
2011	Vasikaran S, Eastell R, Bruyère O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA, Cooper C, Kanis JA; OF-IFCC Bone Marker Standards Working Group. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. February 2011;22(2):391-420.
2002	Seeman E. Pathogenesis of bone fragility in women and men. Lancet. May 25, 2002;359(9320):1841-1850.
2009	Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. February 4, 2009;301(5):513-521.
1998	Khosla S, Melton LJ III, Atkinson EJ, O’Fallon WM, Klee GG, Riggs BL. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab. July 1998;83(7):2266-2274.

Cited By (2)

Year	Entry
2021	Hiam D, Landen S, Jacques M, Voisin S, Alvarez-Romero J, Byrnes E, Chubb P, Levinger I, Eynon N. Osteocalcin and its forms respond similarly to exercise in males and females. Bone. March 2021;144:115818.
2022	Smith C, Hiam D, Tacey A, Lin X, Woessner MN, Zarekookandeh N, Garnham A, Chubb P, Lewis JR, Sim M, Herrmann M, Duque G, Levinger I. Higher bone remodeling biomarkers are related to a higher muscle function in older adults: effects of acute exercise. Bone. December 2022;165:116545.