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Journal of Orthopaedic Science

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01-09-2011 | Original Article

Women with insufficient 25-hydroxyvitamin D without secondary hyperparathyroidism have altered bone turnover and greater incidence of vertebral fractures

Authors: Shota Ikegami, Mikio Kamimura, Shigeharu Uchiyama, Hiroyuki Kato

Published in: Journal of Orthopaedic Science | Issue 5/2011

Abstract

Background

The connection of 25-hydroxyvitamin D [25(OH)D] with bone metabolism is reported to occur indirectly through parathyroid hormone (PTH) activity. However, we hypothesized that 25(OH)D insufficiency raises the risk of bone fracture independent of PTH, since 25(OH)D insufficiency is not always accompanied by hyperparathyroidism. The aim of this study was to show a direct association between 25(OH)D, bone turnover markers, and fractures that was independent of PTH.

Methods

We measured serum 25(OH)D in a group of 330 postmenopausal osteoporotic women who did not have secondary hyperparathyroidism. We analyzed the effects of 25(OH)D insufficiency [25(OH)D < 20 ng/mL] on the expression of several bone markers, including serum bone alkaline phosphatase (BAP), osteocalcin (OC), urinary N-terminal telopeptide of type-I collagen and free deoxypyridinoline (DPD), and inorganic phosphorus (IP), as well as on the prevalence of vertebral fractures.

Results

OC/BAP ratios and IP levels were significantly lower and DPD was significantly higher in 25(OH)D insufficient patients. These effects were independent of age, PTH, and estimated glomerular filtration rate (eGFR). 25(OH)D insufficiency, a low OC/BAP ratio, and low IP were related to the presence of prior vertebral fractures independent of PTH, bone mineral density (BMD), and eGFR.

Conclusions

We propose that 25(OH)D insufficiency is associated with a low OC/BAP ratio and high DPD in postmenopausal osteoporosis patients without hyperparathyroidism. This pathological condition is associated with an increased incidence of prior vertebral fractures independent of PTH, BMD, and eGFR.

Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338(12):777–83.PubMedCrossRef

Sahota O, Mundey MK, San P, Godber IM, Lawson N, Hosking DJ. The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone. 2004;35(1):312–9.PubMedCrossRef

Adami S, Viapiana O, Gatti D, Idolazzi L, Rossini M. Relationship between serum parathyroid hormone, vitamin D sufficiency, age, and calcium intake. Bone. 2008;42(2):267–70.PubMedCrossRef

Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996;11(3):337–49.PubMedCrossRef

Brazier M, Kamel S, Maamer M, Agbomson F, Elesper I, Garabedian M, Desmet G, Sebert JL. Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction. J Bone Miner Res. 1995;10(11):1753–61.PubMedCrossRef

Ooms ME, Lips P, Roos JC, van der Vijgh WJ, Popp-Snijders C, Bezemer PD, Bouter LM. Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. J Bone Miner Res. 1995;10(8):1177–84.PubMedCrossRef

Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Brart G, Meunier PJ, Delmas PD. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res. 1996;11(10):1531–8.PubMedCrossRef

Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res. 2000;15(8):1526–36.PubMedCrossRef

Jesudason D, Need AG, Horowitz M, O’Loughlin PD, Morris HA, Nordin BE. Relationship between serum 25-hydroxyvitamin D and bone resorption markers in vitamin D insufficiency. Bone. 2002;31(5):626–30.PubMedCrossRef

10.

Adami S, Bertoldo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Battista Rini G. 25-Hydroxy vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone. 2009;45(3):423–6.

11.

Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T. Serum osteocalcin/bone-specific alkaline phosphatase ration is a predictor for the presence of vertebral fractures in men with type 2 diabetes. Calcif Tissue Int. 2009;85:228–34.

12.

Owen TA, Aronow M, Shalhoub V, Barone LM, Wilming L, Tassinari MS, Kennedy MB, Pockwinse S, Lian JB, Stein GS. Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J Cell Physiol. 1990;143(3):420–30.PubMedCrossRef

13.

Sakuma M, Endo N, Oinuma T, Hayami T, Endo E, Yazawa T, Watanabe K, Watanabe S. Vitamin D and intact PTH status in patients with hip fracture. Osteoporos Int. 2006;17(11):1608–14.PubMedCrossRef

14.

Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K. Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos Int. 2005;16(11):1425–31.PubMedCrossRef

15.

Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169(6):551–61.PubMedCrossRef

16.

Orimo H. Japanese guidelines for the prevention and treatment of osteoporosis, 2006 edition. Tokyo: Life Science Publishing; 2006.

17.

Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999;282(14):1344–52.PubMedCrossRef

18.

Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16(7):713–6.PubMedCrossRef

19.

Kuchuk NO, Pluijm SM, van Schoor NM, Looman CW, Smit JH, Lips P. Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab. 2009;94(4):1244–50.PubMedCrossRef

20.

Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr. 2003;89(5):552–72.PubMedCrossRef

21.

Gerdhem P, Isaksson A, Akesson K, Obrant KJ. Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Osteoporos Int. 2005;16(12):1506–12.PubMedCrossRef

22.

Knekt P, Laaksonen M, Mattila C, Hrknen T, Marniemi J, Helivaara M, Rissanen H, Montonen J, Reunanen A. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. 2008;19(5):666–71.PubMedCrossRef

23.

Michos ED. Vitamin D deficiency and the risk of incident type 2 diabetes. Future Cardiol. 2009;5(1):15–8.PubMedCrossRef

24.

Santori C, Ceccanti M, Diacinti D, Attilia ML, Toppo L, D’Erasmo E, Romagnoli E, Mascia ML, Cipriani C, Prastaro A, Carnevale V, Minisola S. Skeletal turnover, bone mineral density, and fractures in male chronic abusers of alcohol. J Endocrinol Invest. 2008;31(4):321–6.PubMed

25.

Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998;95(7):3597–602.PubMedCrossRef

26.

Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS 3rd, Frankel WN, Lee SY, Choi Y. TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J Biol Chem. 1997;272(40):25190–4.PubMedCrossRef

27.

Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997;390(6656):175–9.PubMedCrossRef

28.

Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 1999;20(3):345–57.PubMedCrossRef

29.

Takasu H, Sugita A, Uchiyama Y, Katagiri N, Okazaki M, Ogata E, Ikeda K. c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs. J Clin Invest. 2006;116(2):528–35.PubMedCrossRef

30.

Shibata T, Shira-Ishi A, Sato T, Masaki T, Masuda A, Hishiya A, Ishikura N, Higashi S, Uchida Y, Saito MO, Ito M, Ogata E, Watanabe K, Ikeda K. Vitamin D hormone inhibits osteoclastogenesis in vivo by decreasing the pool of osteoclast precursors in bone marrow. J Bone Miner Res. 2002;17(4):622–9.PubMedCrossRef

Title: Women with insufficient 25-hydroxyvitamin D without secondary hyperparathyroidism have altered bone turnover and greater incidence of vertebral fractures
Authors: Shota Ikegami
Mikio Kamimura
Shigeharu Uchiyama
Hiroyuki Kato
Publication date: 01-09-2011
Publisher: Springer Japan
Published in: Journal of Orthopaedic Science / Issue 5/2011
Print ISSN: 0949-2658
Electronic ISSN: 1436-2023
DOI: https://doi.org/10.1007/s00776-011-0107-6

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Women with insufficient 25-hydroxyvitamin D without secondary hyperparathyroidism have altered bone turnover and greater incidence of vertebral fractures

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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