Advertisement

The Endocrine Role of Bone in Cardiometabolic Health

  • Rosemary DeLuccia
  • May Cheung
  • Rohit Ramadoss
  • Abeer Aljahdali
  • Deeptha SukumarEmail author
Cardiovascular Disease (JHY Wu, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cardiovascular Disease

Abstract

Purpose of Review

The purpose of this review is to discuss the current knowledge about major bone regulating hormones vitamin D, parathyroid hormone (PTH), estrogen and bone metabolism markers osteocalcin (OC), bone-specific alkaline phosphatase (BAP), N-terminal propeptide of type 1 collagen (P1NP), and c-terminal type 1 collagen (CTX) and their mechanistic effects on cardiometabolic health.

Recent Findings

Bone regulating hormones, nutrients, and turnover markers influence different aspects of cardiometabolic health including body composition, cardiovascular function, and glycemic control. While most observational research supports a relationship between bone as an endocrine organ and cardiometabolic outcomes, there are limited human clinical trials to strengthen a causal link between the two.

Summary

While the associations between bone and cardiometabolic health are beginning to be understood based on findings from large observations studies, further exploration of bone’s causal influence on health outcomes in humans and the underlying mechanisms of effect are necessary.

Keywords

Bone Cardiometabolic health Bone turnover Body composition Glycemic control Cardiovascular disease 

Notes

Funding Information

No funding or sponsorship was received for this paper.

Compliance with Ethical Standards

Conflict of Interest

Rosemary DeLuccia, May Cheung, Rohit Ramadoss, Abeer Aljahdali, and Deeptha Sukumar declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Fernandes TAP, Goncalves LML, Brito JAA. Relationships between bone turnover and energy metabolism. J Diabetes Res. 2017;2017:9021314.  https://doi.org/10.1155/2017/9021314.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Oldknow KJ, MacRae VE, Farquharson C. Endocrine role of bone: recent and emerging perspectives beyond osteocalcin. J Endocrinol. 2015;225(1):R1–19.  https://doi.org/10.1530/joe-14-0584.CrossRefPubMedGoogle Scholar
  3. 3.
    Suchacki KJ, Roberts F, Lovdel A, Farquharson C, Morton NM, MacRae VE, et al. Skeletal energy homeostasis: a paradigm of endocrine discovery. J Endocrinol. 2017;234(1):R67–r79.  https://doi.org/10.1530/joe-17-0147.CrossRefPubMedGoogle Scholar
  4. 4.
    Sung CC, Liao MT, Lu KC, Wu CC. Role of vitamin D in insulin resistance. J Biomed Biotechnol. 2012;2012:634195.  https://doi.org/10.1155/2012/634195.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Parker J, Hashmi O, Dutton D, Mavrodaris A, Stranges S, Kandala NB, et al. Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas. 2010;65(3):225–36.  https://doi.org/10.1016/j.maturitas.2009.12.013.CrossRefPubMedGoogle Scholar
  6. 6.
    Parikh SJ, Edelman M, Uwaifo GI, Freedman RJ, Semega-Janneh M, Reynolds J, et al. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab. 2004;89(3):1196–9.  https://doi.org/10.1210/jc.2003-031398.CrossRefPubMedGoogle Scholar
  7. 7.
    Salehpour A, Hosseinpanah F, Shidfar F, Vafa M, Razaghi M, Dehghani S, et al. A 12-week double-blind randomized clinical trial of vitamin D(3) supplementation on body fat mass in healthy overweight and obese women. Nutr J. 2012;11:78.  https://doi.org/10.1186/1475-2891-11-78.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–29.  https://doi.org/10.1016/j.chembiol.2013.12.016.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mason C, Tapsoba JD, Duggan C, Imayama I, Wang CY, Korde L, et al. Effects of vitamin D3 supplementation on lean mass, muscle strength, and bone mineral density during weight loss: a double-blind randomized controlled trial. J Am Geriatr Soc. 2016;64(4):769–78.  https://doi.org/10.1111/jgs.14049.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10•.
    Bislev LS, Langagergaard Rodbro L, Rolighed L, Sikjaer T, Rejnmark L. Effects of vitamin D3 supplementation on muscle strength, mass, and physical performance in women with vitamin D insufficiency: a randomized placebo-controlled trial. Calcif Tissue Int. 2018.  https://doi.org/10.1007/s00223-018-0443-z. This randomized placebo-controlled trial examined the effects of vitamin D3 supplementation on muscle strength, physical performance, postural stability, well-being, and quality of life in healthy postmenopausal women with poor vitamin D status, and determined nonsignificant unfavorable outcomes of vitamin D3 supplementation on muscle strength and physical performance, and no beneficial effects on any additional outcomes.
  11. 11.
    Szlagatys-Sidorkiewicz A, Brzezinski M, Jankowska A, Metelska P, Slominska-Fraczek M, Socha P. Long-term effects of vitamin D supplementation in vitamin D deficient obese children participating in an integrated weight-loss programme (a double-blind placebo-controlled study) - rationale for the study design. BMC Pediatr. 2017;17(1):97.  https://doi.org/10.1186/s12887-017-0851-7.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12•.
    Karefylakis C, Sarnblad S, Ariander A, Ehlersson G, Rask E, Rask P. Effect of Vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men-a randomized controlled trial. Endocrine. 2018;61(3):388–97.  https://doi.org/10.1007/s12020-018-1665-6. This prospective placebo-controlled, double blinded, randomized trial of overweight/obese men with vitamin D deficiency determined that 2000 IU of cholecalciferol given over 6 months resulted in no significant improvements in body composition.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Strange RC, Shipman KE, Ramachandran S. Metabolic syndrome: a review of the role of vitamin D in mediating susceptibility and outcome. World J Diabetes. 2015;6(7):896–911.  https://doi.org/10.4239/wjd.v6.i7.896.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Mitri J, Dawson-Hughes B, Hu FB, Pittas AG. Effects of vitamin D and calcium supplementation on pancreatic beta cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the calcium and vitamin D for diabetes mellitus (CaDDM) randomized controlled trial. Am J Clin Nutr. 2011;94(2):486–94.  https://doi.org/10.3945/ajcn.111.011684.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Nagpal J, Pande JN, Bhartia A. A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Diabet Med. 2009;26(1):19–27.  https://doi.org/10.1111/j.1464-5491.2008.02636.x.CrossRefPubMedGoogle Scholar
  16. 16•.
    Trummer C, Theiler-Schwetz V, Kollmann M, Wolfler M, Munzker J, Pilz S, et al. Effects of vitamin D supplementation on metabolic and endocrine parameters in healthy premenopausal women: a randomized controlled trial. Clin Nutr (Edinburgh, Scotland). 2019.  https://doi.org/10.1016/j.clnu.2019.03.007. This double-blind, randomized placebo-controlled trial conducted in premenopausal women with poor vitamin D status determined that 20,000 IU of cholecalciferol given over 24 weeks resulted in a significant effect on the homeostatic model assessment-insulin resistance (HOMA-IR) and the quantitative-insulin-sensitivity check index (QUICKI), supporting improved endocrine functioning.
  17. 17.
    George PS, Pearson ER, Witham MD. Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta-analysis. Diabet Med. 2012;29(8):e142–50.  https://doi.org/10.1111/j.1464-5491.2012.03672.x.CrossRefPubMedGoogle Scholar
  18. 18.
    Legarth C, Grimm D, Wehland M, Bauer J, Kruger M. The Impact of Vitamin D in the Treatment of Essential Hypertension. International journal of molecular sciences. 2018;19(2).  https://doi.org/10.3390/ijms19020455.
  19. 19.
    Chen S, Sun Y, Agrawal DK. Vitamin D deficiency and essential hypertension. J Am Soc Hypertens. 2015;9(11):885–901.  https://doi.org/10.1016/j.jash.2015.08.009.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Elamin MB, Abu Elnour NO, Elamin KB, Fatourechi MM, Alkatib AA, Almandoz JP, et al. Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(7):1931–42.  https://doi.org/10.1210/jc.2011-0398.CrossRefPubMedGoogle Scholar
  21. 21.
    Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, et al. Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data. JAMA Intern Med. 2015;175(5):745–54.  https://doi.org/10.1001/jamainternmed.2015.0237.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kassi E, Adamopoulos C, Basdra EK, Papavassiliou AG. Role of vitamin D in atherosclerosis. Circulation. 2013;128(23):2517–31.  https://doi.org/10.1161/circulationaha.113.002654.CrossRefPubMedGoogle Scholar
  23. 23.
    Skaaby T, Husemoen LL, Martinussen T, Thyssen JP, Melgaard M, Thuesen BH, et al. Vitamin D status, filaggrin genotype, and cardiovascular risk factors: a Mendelian randomization approach. PLoS One. 2013;8(2):e57647.  https://doi.org/10.1371/journal.pone.0057647.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Favus MJ, Goltzman D. Regulation of calcium and magnesium. Hoboken: John Wiley & Sons, Inc.; 2013.CrossRefGoogle Scholar
  25. 25.
    Nissenson RAJ, Juppner H. Parathyroid Hormone. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Hoboken: John Wiley & Sons, Inc.; 2013. p. 208–14.CrossRefGoogle Scholar
  26. 26.
    Potts JT. Parathyroid hormone: past and present. J Endocrinol. 2005;187(3):311–25.  https://doi.org/10.1677/joe.1.06057.CrossRefPubMedGoogle Scholar
  27. 27.
    Bikle DD. Vitamin D and bone. Curr Osteoporos Rep. 2012;10(2):151–9.  https://doi.org/10.1007/s11914-012-0098-z.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Cannata-Andia JB, Carrera F. The Pathophysiology of Secondary Hyperparathyroidism and the Consequences of Uncontrolled Mineral Metabolism in Chronic Kidney Disease: The Role of COSMOS. NDT Plus. 2008;1(Suppl 1):i2–6.  https://doi.org/10.1093/ndtplus/sfm037.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Rashid G, Bernheim J, Green J, Benchetrit S. Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways. Am J Physiol Ren Physiol. 2007;292(4):F1215–8.  https://doi.org/10.1152/ajprenal.00406.2006.CrossRefGoogle Scholar
  30. 30.
    Bell NH, Epstein S, Greene A, Shary J, Oexmann MJ, Shaw S. Evidence for alteration of the vitamin D-endocrine system in obese subjects. J Clin Invest. 1985;76(1):370–3.  https://doi.org/10.1172/jci111971.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Bolland MJ, Grey AB, Ames RW, Horne AM, Gamble GD, Reid IR. Fat mass is an important predictor of parathyroid hormone levels in postmenopausal women. Bone. 2006;38(3):317–21.  https://doi.org/10.1016/j.bone.2005.08.018.CrossRefPubMedGoogle Scholar
  32. 32.
    Saab G, Whaley-Connell A, McFarlane SI, Li S, Chen SC, Sowers JR, et al. Obesity is associated with increased parathyroid hormone levels independent of glomerular filtration rate in chronic kidney disease. Metab Clin Exp. 2010;59(3):385–9.  https://doi.org/10.1016/j.metabol.2009.08.007.CrossRefPubMedGoogle Scholar
  33. 33.
    Marwaha RK, Garg MK, Mahalle N, Bhadra K, Tandon N. Role of parathyroid hormone in determination of fat mass in patients with vitamin D deficiency. Indian J Endocrinol Metabol. 2017;21(6):848–53.  https://doi.org/10.4103/ijem.IJEM_42_17.CrossRefGoogle Scholar
  34. 34.
    Querfeld U, Hoffmann MM, Klaus G, Eifinger F, Ackerschott M, Michalk D, et al. Antagonistic effects of vitamin D and parathyroid hormone on lipoprotein lipase in cultured adipocytes. J Am Soc Nephrol. 1999;10(10):2158–64.PubMedGoogle Scholar
  35. 35.
    Reusch JE, Sussman KE, Draznin B. Inverse relationship between GLUT-4 phosphorylation and its intrinsic activity. J Biol Chem. 1993;268(5):3348–51.PubMedGoogle Scholar
  36. 36.
    Lotito A, Teramoto M, Cheung M, Becker K, Sukumar D. Serum parathyroid hormone responses to vitamin D supplementation in overweight/obese adults: a systematic review and meta-analysis of randomized clinical trials. Nutrients. 2017;9(3).  https://doi.org/10.3390/nu9030241.
  37. 37.
    Lotfi-Dizaji L, Mahboob S, Aliashrafi S, Vaghef-Mehrabany E, Ebrahimi-Mameghani M, Morovati A. Effect of vitamin D supplementation along with weight loss diet on meta-inflammation and fat mass in obese subjects with vitamin D deficiency: a double-blind placebo-controlled randomized clinical trial. Clin Endocrinol. 2019;90(1):94–101.  https://doi.org/10.1111/cen.13861.CrossRefGoogle Scholar
  38. 38•.
    Valente-Da-Silva HG, Maya MCA, Moreira AS. Parathyroidectomy in chronic kidney disease: effects on weight gain and on quality of life improvement. Revista do Colegio Brasileiro de Cirurgioes. 2017;44(3):263–9.  https://doi.org/10.1590/0100-69912017003007. This longitudinal study of hemodialysis patients with severe secondary parathyroidism demonstrated that parathyroidectomy resulted in significant increases in body weight and body cell mass with stabilization of intact parathyroid hormone concentrations after surgery.CrossRefPubMedGoogle Scholar
  39. 39.
    Gunther CW, Legowski PA, Lyle RM, Weaver CM, McCabe LD, McCabe GP, et al. Parathyroid hormone is associated with decreased fat mass in young healthy women. Int J Obes. 2006;30(1):94–9.  https://doi.org/10.1038/sj.ijo.0803066.CrossRefGoogle Scholar
  40. 40.
    Ishimura E, Okuno S, Tsuboniwa N, Norimine K, Fukumoto S, Yamakawa K, et al. Significant positive association between parathyroid hormone and fat mass and lean mass in chronic hemodialysis patients. J Clin Endocrinol Metab. 2013;98(3):1264–70.  https://doi.org/10.1210/jc.2012-3883.CrossRefPubMedGoogle Scholar
  41. 41.
    Kimura S, Yoshioka K. Parathyroid hormone and parathyroid hormone type-1 receptor accelerate myocyte differentiation. Sci Rep. 2014;4:5066.  https://doi.org/10.1038/srep05066.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766–72.  https://doi.org/10.1210/jc.2003-030604.CrossRefPubMedGoogle Scholar
  43. 43.
    Pilz S, Tomaschitz A, Drechsler C, Ritz E, Boehm BO, Grammer TB, et al. Parathyroid hormone level is associated with mortality and cardiovascular events in patients undergoing coronary angiography. Eur Heart J. 2010;31(13):1591–8.  https://doi.org/10.1093/eurheartj/ehq109.CrossRefPubMedGoogle Scholar
  44. 44.
    Morley P, Whitfield JF, Willick GE. Parathyroid hormone: an anabolic treatment for osteoporosis. Curr Pharm Des. 2001;7(8):671–87.CrossRefPubMedGoogle Scholar
  45. 45.
    Goettsch C, Iwata H, Aikawa E. Parathyroid hormone: critical bridge between bone metabolism and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2014;34(7):1333–5.  https://doi.org/10.1161/atvbaha.114.303637.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Coen G, Calabria S, Bellinghieri G, Pecchini F, Conte F, Chiappini MG, et al. Parathyroidectomy in chronic renal failure: short- and long-term results on parathyroid function, blood pressure and anemia. Nephron. 2001;88(2):149–55.  https://doi.org/10.1159/000045976.CrossRefPubMedGoogle Scholar
  47. 47.
    Heyliger A, Tangpricha V, Weber C, Sharma J. Parathyroidectomy decreases systolic and diastolic blood pressure in hypertensive patients with primary hyperparathyroidism. Surgery. 2009;146(6):1042–7.  https://doi.org/10.1016/j.surg.2009.09.024.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Ishay A, Herer P, Luboshitzky R. Effects of successful parathyroidectomy on metabolic cardiovascular risk factors in patients with severe primary hyperparathyroidism. Endocr Pract. 2011;17(4):584–90.  https://doi.org/10.4158/ep10321.Or.CrossRefPubMedGoogle Scholar
  49. 49.
    Akpunonu BE, Mulrow PJ, Hoffman EA. Secondary hypertension: evaluation and treatment. Dis Mon. 1996;42(10):609–722.CrossRefPubMedGoogle Scholar
  50. 50.
    Brown J, de Boer IH, Robinson-Cohen C, Siscovick DS, Kestenbaum B, Allison M, et al. Aldosterone, parathyroid hormone, and the use of renin-angiotensin-aldosterone system inhibitors: the multi-ethnic study of atherosclerosis. J Clin Endocrinol Metab. 2015;100(2):490–9.  https://doi.org/10.1210/jc.2014-3949.CrossRefPubMedGoogle Scholar
  51. 51.
    Maniero C, Fassina A, Seccia TM, Toniato A, Iacobone M, Plebani M, et al. Mild hyperparathyroidism: a novel surgically correctable feature of primary aldosteronism. J Hypertens. 2012;30(2):390–5.  https://doi.org/10.1097/HJH.0b013e32834f0451.CrossRefPubMedGoogle Scholar
  52. 52.
    Pilz S, Kienreich K, Drechsler C, Ritz E, Fahrleitner-Pammer A, Gaksch M, et al. Hyperparathyroidism in patients with primary aldosteronism: cross-sectional and interventional data from the GECOH study. J Clin Endocrinol Metab. 2012;97(1):E75–9.  https://doi.org/10.1210/jc.2011-2183.CrossRefPubMedGoogle Scholar
  53. 53.
    Rossi E, Sani C, Perazzoli F, Casoli MC, Negro A, Dotti C. Alterations of calcium metabolism and of parathyroid function in primary aldosteronism, and their reversal by spironolactone or by surgical removal of aldosterone-producing adenomas. Am J Hypertens. 1995;8(9):884–93.  https://doi.org/10.1016/0895-7061(95)00182-o.CrossRefPubMedGoogle Scholar
  54. 54.
    Neves KR, Graciolli FG, dos Reis LM, Graciolli RG, Neves CL, Magalhaes AO, et al. Vascular calcification: contribution of parathyroid hormone in renal failure. Kidney Int. 2007;71(12):1262–70.  https://doi.org/10.1038/sj.ki.5002241.CrossRefPubMedGoogle Scholar
  55. 55.
    Nilsson IL, Rastad J, Johansson K, Lind L. Endothelial vasodilatory function and blood pressure response to local and systemic hypercalcemia. Surgery. 2001;130(6):986–90.  https://doi.org/10.1067/msy.2001.118368.CrossRefPubMedGoogle Scholar
  56. 56.
    Rambausek M, Ritz E, Rascher W, Kreusser W, Mann JF, Kreye VA, et al. Vascular effects of parathyroid hormone (PTH). Adv Exp Med Biol. 1982;151:619–32.CrossRefPubMedGoogle Scholar
  57. 57.
    Fliser D, Franek E, Fode P, Stefanski A, Schmitt CP, Lyons M, et al. Subacute infusion of physiological doses of parathyroid hormone raises blood pressure in humans. Nephrol Dial Transplant. 1997;12(5):933–8.CrossRefPubMedGoogle Scholar
  58. 58.
    Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab. 2001;86(4):1633–7.  https://doi.org/10.1210/jcem.86.4.7393.CrossRefPubMedGoogle Scholar
  59. 59.
    Pilz S, Gaksch M, Kienreich K, Grubler M, Verheyen N, Fahrleitner-Pammer A, et al. Effects of vitamin D on blood pressure and cardiovascular risk factors: a randomized controlled trial. Hypertension (Dallas, Tex : 1979). 2015;65(6):1195–201.  https://doi.org/10.1161/hypertensionaha.115.05319.CrossRefGoogle Scholar
  60. 60.
    Wannamethee SG, Welsh P, Papacosta O, Lennon L, Whincup PH, Sattar N. Elevated parathyroid hormone, but not vitamin D deficiency, is associated with increased risk of heart failure in older men with and without cardiovascular disease. Circ Heart Fail. 2014;7(5):732–9.  https://doi.org/10.1161/circheartfailure.114.001272.CrossRefPubMedGoogle Scholar
  61. 61.
    van Hoek M, Dallinga-Thie GM, Steyerberg EW, Sijbrands EJ. Diagnostic value of post-heparin lipase testing in detecting common genetic variants in the LPL and LIPC genes. Eur J Hum Genet. 2009;17(11):1386–93.  https://doi.org/10.1038/ejhg.2009.61.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Klop B, Elte JW, Cabezas MC. Dyslipidemia in obesity: mechanisms and potential targets. Nutrients. 2013;5(4):1218–40.  https://doi.org/10.3390/nu5041218.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Parfitt AM. The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone diseases. II. PTH and bone cells: bone turnover and plasma calcium regulation. Metab Clin Exp. 1976;25(8):909–55.CrossRefPubMedGoogle Scholar
  64. 64.
    Hagstrom E, Lundgren E, Rastad J, Hellman P. Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening. Eur J Endocrinol. 2006;155(1):33–9.  https://doi.org/10.1530/eje.1.02173.CrossRefPubMedGoogle Scholar
  65. 65.
    Zanos S, Mitsopoulos E, Sakellariou G. Parathyroid hormone levels, calcium-channel blockers, and the dyslipidemia of nondiabetic hemodialysis patients. Ren Fail. 2005;27(2):163–9.CrossRefPubMedGoogle Scholar
  66. 66.
    Norenstedt S, Pernow Y, Brismar K, Saaf M, Ekip A, Granath F, et al. Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study. Eur J Endocrinol. 2013;169(6):795–804.  https://doi.org/10.1530/eje-13-0547.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Rolighed L, Rejnmark L, Sikjaer T, Heickendorff L, Vestergaard P, Mosekilde L, et al. Vitamin D treatment in primary hyperparathyroidism: a randomized placebo controlled trial. J Clin Endocrinol Metab. 2014;99(3):1072–80.  https://doi.org/10.1210/jc.2013-3978.CrossRefPubMedGoogle Scholar
  68. 68.
    Shah VN, Shah CS, Bhadada SK, Rao DS. Effect of 25 (OH) D replacements in patients with primary hyperparathyroidism (PHPT) and coexistent vitamin D deficiency on serum 25(OH) D, calcium and PTH levels: a meta-analysis and review of literature. Clin Endocrinol. 2014;80(6):797–803.  https://doi.org/10.1111/cen.12398.CrossRefGoogle Scholar
  69. 69.
    Jorde R, Szumlas K, Haug E, Sundsfjord J. The effects of calcium supplementation to patients with primary hyperparathyroidism and a low calcium intake. Eur J Nutr. 2002;41(6):258–63.  https://doi.org/10.1007/s00394-002-0383-1.CrossRefPubMedGoogle Scholar
  70. 70.
    Richards ML, Thompson NW. Diabetes mellitus with hyperparathyroidism: another indication for parathyroidectomy? Surgery. 1999;126(6):1160–6.CrossRefPubMedGoogle Scholar
  71. 71.
    Schaerstrom R, Hamfelt A, Soderhjelm L. Parathyroid hormone and calcitonin in diabetes mellitus. Ups J Med Sci. 1986;91(1):99–104.CrossRefPubMedGoogle Scholar
  72. 72.
    Wongsurawat N, Armbrecht HJ, Siegel NA. Effects of diabetes mellitus on parathyroid hormone-stimulated protein kinase activity, ferredoxin phosphorylation, and renal 1,25-dihydroxyvitamin D production. J Lab Clin Med. 1991;117(4):319–24.PubMedGoogle Scholar
  73. 73.
    Fadda GZ, Akmal M, Lipson LG, Massry SG. Direct effect of parathyroid hormone on insulin secretion from pancreatic islets. Am J Phys. 1990;258(6 Pt 1):E975–84.  https://doi.org/10.1152/ajpendo.1990.258.6.E975.CrossRefGoogle Scholar
  74. 74.
    Saxe AW, Gibson G, Gingerich RL, Levy J. Parathyroid hormone decreases in vivo insulin effect on glucose utilization. Calcif Tissue Int. 1995;57(2):127–32.CrossRefPubMedGoogle Scholar
  75. 75.
    Chang E, Donkin SS, Teegarden D. Parathyroid hormone suppresses insulin signaling in adipocytes. Mol Cell Endocrinol. 2009;307(1–2):77–82.  https://doi.org/10.1016/j.mce.2009.03.024.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Rhee CM, Leung AM, Kovesdy CP, Lynch KE, Brent GA, Kalantar-Zadeh K. Updates on the management of diabetes in dialysis patients. Semin Dial. 2014;27(2):135–45.  https://doi.org/10.1111/sdi.12198.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007;30(4):980–6.  https://doi.org/10.2337/dc06-1994.CrossRefPubMedGoogle Scholar
  78. 78.
    Meyer MR, Clegg DJ, Prossnitz ER, Barton M. Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors. Acta Physiol (Oxford, England). 2011;203(1):259–69.  https://doi.org/10.1111/j.1748-1716.2010.02237.x.CrossRefGoogle Scholar
  79. 79.
    Wise PM, Suzuki S, Brown CM. Estradiol: a hormone with diverse and contradictory neuroprotective actions. Dialogues Clin Neurosci. 2009;11(3):297–303.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Vrtacnik P, Ostanek B, Mencej-Bedrac S, Marc J. The many faces of estrogen signaling. Biochem Med. 2014;24(3):329–42.  https://doi.org/10.11613/bm.2014.035.CrossRefGoogle Scholar
  81. 81.
    Oursler MJ, Osdoby P, Pyfferoen J, Riggs BL, Spelsberg TC. Avian osteoclasts as estrogen target cells. Proc Natl Acad Sci U S A. 1991;88(15):6613–7.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocr Rev. 2008;29(4):441–64.  https://doi.org/10.1210/er.2008-0002.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Kousteni S, Bellido T, Plotkin LI, O’Brien CA, Bodenner DL, Han L, et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell. 2001;104(5):719–30.PubMedGoogle Scholar
  84. 84.
    Quinton ND, Smith RF, Clayton PE, Gill MS, Shalet S, Justice SK, et al. Leptin binding activity changes with age: the link between leptin and puberty. J Clin Endocrinol Metab. 1999;84(7):2336–41.  https://doi.org/10.1210/jcem.84.7.5834.CrossRefPubMedGoogle Scholar
  85. 85.
    Ainslie DA, Morris MJ, Wittert G, Turnbull H, Proietto J, Thorburn AW. Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y. Int J Obes Relat Metab Disord. 2001;25(11):1680–8.  https://doi.org/10.1038/sj.ijo.0801806.CrossRefPubMedGoogle Scholar
  86. 86.
    Shi H, Clegg DJ. Sex differences in the regulation of body weight. Physiol Behav. 2009;97(2):199–204.  https://doi.org/10.1016/j.physbeh.2009.02.017.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Norman RJ, Flight IH, Rees MC. Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution. Cochrane Database Syst Rev. 2000;(2):Cd001018.  https://doi.org/10.1002/14651858.Cd001018.
  88. 88.
    Ziaei S, Moaya M, Faghihzadeh S. Comparative effects of continuous combined hormone therapy and tibolone on body composition in postmenopausal women. Climacteric. 2010;13(3):249–53.  https://doi.org/10.3109/13697130903318240.CrossRefPubMedGoogle Scholar
  89. 89.
    Bea JW, Zhao Q, Cauley JA, LaCroix AZ, Bassford T, Lewis CE, et al. Effect of hormone therapy on lean body mass, falls, and fractures: 6-year results from the Women’s Health Initiative hormone trials. Menopause (New York, NY). 2011;18(1):44–52.  https://doi.org/10.1097/gme.0b013e3181e3aab1.CrossRefGoogle Scholar
  90. 90.
    Dubey RK, Oparil S, Imthurn B, Jackson EK. Sex hormones and hypertension. Cardiovasc Res. 2002;53(3):688–708.CrossRefPubMedGoogle Scholar
  91. 91.
    Cacciatore B, Paakkari I, Hasselblatt R, Nieminen MS, Toivonen J, Tikkanen MI, et al. Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women. Am J Obstet Gynecol. 2001;184(5):904–9.  https://doi.org/10.1067/mob.2001.111246.CrossRefPubMedGoogle Scholar
  92. 92.
    Utian WH. Effect of postmenopausal estrogen therapy on diastolic blood pressure and bodyweight. Maturitas. 1978;1(1):3–8.CrossRefPubMedGoogle Scholar
  93. 93.
    Lam KK, Hu CT, Ou TY, Yen MH, Chen HI. Effects of oestrogen replacement on steady and pulsatile haemodynamics in ovariectomized rats. Br J Pharmacol. 2002;136(6):811–8.  https://doi.org/10.1038/sj.bjp.0704762.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Colafella KMM, Denton KM. Sex-specific differences in hypertension and associated cardiovascular disease. Nat Rev Nephrol. 2018;14(3):185–201.  https://doi.org/10.1038/nrneph.2017.189.CrossRefPubMedGoogle Scholar
  95. 95.
    Brussaard HE, Gevers Leuven JA, Frolich M, Kluft C, Krans HM. Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM. Diabetologia. 1997;40(7):843–9.CrossRefPubMedGoogle Scholar
  96. 96.
    Bailey CJ, Ahmed-Sorour H. Role of ovarian hormones in the long-term control of glucose homeostasis. Effects of insulin secretion. Diabetologia. 1980;19(5):475–81.CrossRefPubMedGoogle Scholar
  97. 97.
    Mauvais-Jarvis F, Clegg DJ, Hevener AL. The role of estrogens in control of energy balance and glucose homeostasis. Endocr Rev. 2013;34(3):309–38.  https://doi.org/10.1210/er.2012-1055.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994;331(16):1056–61.  https://doi.org/10.1056/nejm199410203311604.CrossRefPubMedGoogle Scholar
  99. 99.
    Neve A, Corrado A, Cantatore FP. Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol. 2013;228(6):1149–53.  https://doi.org/10.1002/jcp.24278.CrossRefPubMedGoogle Scholar
  100. 100.
    Research ASfBaM. Primer on the metabolic bone diseases and disorders of mineral metabolism. 8th ed. Hoboken: Wiley-Blackwell; 2013.Google Scholar
  101. 101.
    Zoch ML, Abou DS, Clemens TL, Thorek DL, Riddle RC. In vivo radiometric analysis of glucose uptake and distribution in mouse bone. Bone Res. 2016;4:16004.  https://doi.org/10.1038/boneres.2016.4.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Lian JB, Tassinari M, Glowacki J. Resorption of implanted bone prepared from normal and warfarin-treated rats. J Clin Invest. 1984;73(4):1223–6.  https://doi.org/10.1172/jci111308.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Chenu C, Colucci S, Grano M, Zigrino P, Barattolo R, Zambonin G, et al. Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium-mediated intracellular signaling in human osteoclast-like cells. J Cell Biol. 1994;127(4):1149–58.CrossRefPubMedGoogle Scholar
  104. 104.
    Ingram RT, Park YK, Clarke BL, Fitzpatrick LA. Age- and gender-related changes in the distribution of osteocalcin in the extracellular matrix of normal male and female bone. Possible involvement of osteocalcin in bone remodeling. J Clin Invest. 1994;93(3):989–97.  https://doi.org/10.1172/jci117106.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Bao Y, Ma X, Yang R, Wang F, Hao Y, Dou J, et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J Clin Endocrinol Metab. 2013;98(1):345–51.  https://doi.org/10.1210/jc.2012-2906.CrossRefPubMedGoogle Scholar
  106. 106.
    Zhou M, Ma X, Li H, Pan X, Tang J, Gao Y, et al. Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals. Eur J Endocrinol. 2009;161(5):723–9.  https://doi.org/10.1530/eje-09-0585.CrossRefPubMedGoogle Scholar
  107. 107.
    Schafer AL, Sellmeyer DE, Schwartz AV, Rosen CJ, Vittinghoff E, Palermo L, et al. Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1–84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab. 2011;96(12):E1982–9.  https://doi.org/10.1210/jc.2011-0587.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108•.
    Knapen MHJ, Jardon KM, Vermeer C. Vitamin K-induced effects on body fat and weight: results from a 3-year vitamin K2 intervention study. Eur J Clin Nutr. 2018;72(1):136–41.  https://doi.org/10.1038/ejcn.2017.146. In this randomized placebo-controlled human intervention trial in postmenopausal women, 180 mcg/day of vitamin K2 over 3 years resulted in increased circulating carboxylated osteocalcin, but had no effect on body composition. Additionally, in good responders, vitamin K2 treatment resulted in significantly increased total and human molecular weight adiponectin and decreased abdominal fat mass and estimated viseral adipose tissue area.CrossRefPubMedGoogle Scholar
  109. 109.
    Shea MK, Dawson-Hughes B, Gundberg CM, Booth SL. Reducing undercarboxylated osteocalcin with vitamin k supplementation does not promote lean tissue loss or fat gain over 3 years in older women and men: a randomized controlled trial. J Bone Miner Res. 2017;32(2):243–9.  https://doi.org/10.1002/jbmr.2989.CrossRefPubMedGoogle Scholar
  110. 110.
    Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Beilby JP, et al. Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur J Endocrinol. 2010;163(2):265–72.  https://doi.org/10.1530/eje-10-0414.CrossRefPubMedGoogle Scholar
  111. 111.
    Saleem U, Mosley TH Jr, Kullo IJ. Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arterioscler Thromb Vasc Biol. 2010;30(7):1474–8.  https://doi.org/10.1161/atvbaha.110.204859.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, Yano S, et al. Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2009;94(1):45–9.  https://doi.org/10.1210/jc.2008-1455.CrossRefPubMedGoogle Scholar
  113. 113.
    Goliasch G, Blessberger H, Azar D, Heinze G, Wojta J, Bieglmayer C, et al. Markers of bone metabolism in premature myocardial infarction (</= 40 years of age). Bone. 2011;48(3):622–6.  https://doi.org/10.1016/j.bone.2010.11.005.CrossRefPubMedGoogle Scholar
  114. 114.
    Mansour AG, Hariri E, Daaboul Y, Korjian S, El Alam A, Protogerou AD, et al. Vitamin K2 supplementation and arterial stiffness among renal transplant recipients-a single-arm, single-center clinical trial. J Am Soc Hypertens. 2017;11(9):589–97.  https://doi.org/10.1016/j.jash.2017.07.001.CrossRefPubMedGoogle Scholar
  115. 115.
    Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–69.  https://doi.org/10.1016/j.cell.2007.05.047.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Zanatta LC, Boguszewski CL, Borba VZ, Kulak CA. Osteocalcin, energy and glucose metabolism. Arq Bras Endocrinol Metabol. 2014;58(5):444–51.CrossRefPubMedGoogle Scholar
  117. 117.
    Hwang YC, Jeong IK, Ahn KJ, Chung HY. The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects. Diabetes Metab Res Rev. 2009;25(8):768–72.  https://doi.org/10.1002/dmrr.1045.CrossRefPubMedGoogle Scholar
  118. 118.
    Shea MK, Gundberg CM, Meigs JB, Dallal GE, Saltzman E, Yoshida M, et al. Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr. 2009;90(5):1230–5.  https://doi.org/10.3945/ajcn.2009.28151.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Diaz-Lopez A, Bullo M, Juanola-Falgarona M, Martinez-Gonzalez MA, Estruch R, Covas MI, et al. Reduced serum concentrations of carboxylated and undercarboxylated osteocalcin are associated with risk of developing type 2 diabetes mellitus in a high cardiovascular risk population: a nested case-control study. J Clin Endocrinol Metab. 2013;98(11):4524–31.  https://doi.org/10.1210/jc.2013-2472.CrossRefPubMedGoogle Scholar
  120. 120.
    Boucher-Berry C, Speiser PW, Carey DE, Shelov SP, Accacha S, Fennoy I, et al. Vitamin D, osteocalcin, and risk for adiposity as comorbidities in middle school children. J Bone Miner Res. 2012;27(2):283–93.  https://doi.org/10.1002/jbmr.550.CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Sukumar D, Shapses SA, Schneider SH. Vitamin D supplementation during short-term caloric restriction in healthy overweight/obese older women: effect on glycemic indices and serum osteocalcin levels. Mol Cell Endocrinol. 2015;410:73–7.  https://doi.org/10.1016/j.mce.2015.01.002.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Thrailkill KM, Jo CH, Cockrell GE, Moreau CS, Lumpkin CK Jr, Fowlkes JL. Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes. Osteoporos Int. 2012;23(6):1799–806.  https://doi.org/10.1007/s00198-011-1807-7.CrossRefPubMedGoogle Scholar
  123. 123.
    Masrour Roudsari J, Mahjoub S. Quantification and comparison of bone-specific alkaline phosphatase with two methods in normal and paget’s specimens. Caspian J Intern Med. 2012;3(3):478–83.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Pollmann D, Siepmann S, Geppert R, Wernecke KD, Possinger K, Luftner D. The amino-terminal propeptide (PINP) of type I collagen is a clinically valid indicator of bone turnover and extent of metastatic spread in osseous metastatic breast cancer. Anticancer Res. 2007;27(4a):1853–62.PubMedGoogle Scholar
  125. 125.
    Greenblatt MB, Tsai JN, Wein MN. Bone turnover markers in the diagnosis and monitoring of metabolic bone disease. Clin Chem. 2017;63(2):464–74.  https://doi.org/10.1373/clinchem.2016.259085.CrossRefPubMedGoogle Scholar
  126. 126.
    Ishimura E, Okuno S, Okazaki H, Norimine K, Yamakawa K, Yamakawa T, et al. Significant association between bone-specific alkaline phosphatase and vascular calcification of the hand arteries in male hemodialysis patients. Kidney Blood Press Res. 2014;39(4):299–307.  https://doi.org/10.1159/000355807.CrossRefPubMedGoogle Scholar
  127. 127.
    Rosen HN, Moses AC, Garber J, Iloputaife ID, Ross DS, Lee SL, et al. Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int. 2000;66(2):100–3.CrossRefPubMedGoogle Scholar
  128. 128.
    Viljakainen H, Ivaska KK, Paldanius P, Lipsanen-Nyman M, Saukkonen T, Pietilainen KH, et al. Suppressed bone turnover in obesity: a link to energy metabolism? A case-control study. J Clin Endocrinol Metab. 2014;99(6):2155–63.  https://doi.org/10.1210/jc.2013-3097.CrossRefPubMedGoogle Scholar
  129. 129.
    Kucukalic-Selimovic E, Valjevac A, Hadzovic-Dzuvo A. The utility of procollagen type 1 N-terminal propeptide for the bone status assessment in postmenopausal women. Bosnian J Basic Med Sci. 2013;13(4):259–65.  https://doi.org/10.17305/bjbms.2013.2337.CrossRefGoogle Scholar
  130. 130.
    Cheung CL, Tan KC, Lam KS, Cheung BM. The relationship between glucose metabolism, metabolic syndrome, and bone-specific alkaline phosphatase: a structural equation modeling approach. J Clin Endocrinol Metab. 2013;98(9):3856–63.  https://doi.org/10.1210/jc.2013-2024.CrossRefPubMedGoogle Scholar
  131. 131.
    Iba K, Takada J, Yamashita T. The serum level of bone-specific alkaline phosphatase activity is associated with aortic calcification in osteoporosis patients. J Bone Miner Metab. 2004;22(6):594–6.  https://doi.org/10.1007/s00774-004-0528-9.CrossRefPubMedGoogle Scholar
  132. 132.
    Fukushima N, Suzuki A, Fukushima K, Tanaka Y, Sato Y, Shiga T, et al. Impact of the serum bone-specific alkaline phosphatase level at the initiation of hemodialysis therapy for end-stage renal disease on cardiovascular events. IJC Metab Endocr. 2014;4:58–62.CrossRefGoogle Scholar
  133. 133.
    Drechsler C, Verduijn M, Pilz S, Krediet RT, Dekker FW, Wanner C, et al. Bone alkaline phosphatase and mortality in dialysis patients. Clin J Am Soc Nephrol. 2011;6(7):1752–9.  https://doi.org/10.2215/cjn.10091110.CrossRefPubMedGoogle Scholar
  134. 134.
    Newton A, Hanks L, Judd S, Wallace S, Durant N, Casazza K. Low HDL cholesterol may lead to disruption of bone (re) modeling in obese early pubertal girls. Int J Orthop. 2015;2(3).Google Scholar
  135. 135.
    Anderson JL, Vanwoerkom RC, Horne BD, Bair TL, May HT, Lappe DL, et al. Parathyroid hormone, vitamin D, renal dysfunction, and cardiovascular disease: dependent or independent risk factors? Am Heart J. 2011;162(2):331–9.e2.  https://doi.org/10.1016/j.ahj.2011.05.005.CrossRefPubMedGoogle Scholar
  136. 136.
    Saber LM, Mahran HN, Baghdadi HH, Al Hawsawi ZM. Interrelationship between bone turnover markers, calciotropic hormones and leptin in obese Saudi children. Eur Rev Med Pharmacol Sci. 2015;19(22):4332–43.PubMedGoogle Scholar
  137. 137.
    Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, et al. Adiponectin is associated with changes in bone markers during glycemic control in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2009;94(8):3031–7.  https://doi.org/10.1210/jc.2008-2187.CrossRefPubMedGoogle Scholar
  138. 138.
    Szulc P, Varennes A, Delmas PD, Goudable J, Chapurlat R. Men with metabolic syndrome have lower bone mineral density but lower fracture risk--the MINOS study. J Bone Miner Res. 2010;25(6):1446–54.  https://doi.org/10.1002/jbmr.13.CrossRefPubMedGoogle Scholar
  139. 139.
    Wang J, Yan DD, Hou XH, Bao YQ, Hu C, Zhang ZL, et al. Association of bone turnover markers with glucose metabolism in Chinese population. Acta Pharmacol Sin. 2017;38(12):1611–7.  https://doi.org/10.1038/aps.2017.23.CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Ogata M, Ide R, Takizawa M, Tanaka M, Tetsuo T, Sato A, et al. Association between basal metabolic function and bone metabolism in postmenopausal women with type 2 diabetes. Nutrition (Burbank, Los Angeles County, Calif). 2015;31(11–12):1394–401.  https://doi.org/10.1016/j.nut.2015.06.012.CrossRefGoogle Scholar
  141. 141.
    Oz SG, Guven GS, Kilicarslan A, Calik N, Beyazit Y, Sozen T. Evaluation of bone metabolism and bone mass in patients with type-2 diabetes mellitus. J Natl Med Assoc. 2006;98(10):1598–604.PubMedPubMedCentralGoogle Scholar
  142. 142.
    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.  https://doi.org/10.1007/s00198-005-1877-5.CrossRefPubMedGoogle Scholar
  143. 143.
    Xuan Y, Sun LH, Liu DM, Zhao L, Tao B, Wang WQ, et al. Positive association between serum levels of bone resorption marker CTX and HbA1c in women with normal glucose tolerance. J Clin Endocrinol Metab. 2015;100(1):274–81.  https://doi.org/10.1210/jc.2014-2583.CrossRefPubMedGoogle Scholar
  144. 144.
    Hamilton EJ, Rakic V, Davis WA, Paul Chubb SA, Kamber N, Prince RL, et al. A five-year prospective study of bone mineral density in men and women with diabetes: the Fremantle Diabetes Study. Acta Diabetol. 2012;49(2):153–8.  https://doi.org/10.1007/s00592-011-0324-7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Rosemary DeLuccia
    • 1
  • May Cheung
    • 1
  • Rohit Ramadoss
    • 1
  • Abeer Aljahdali
    • 1
  • Deeptha Sukumar
    • 1
    Email author
  1. 1.Nutrition Sciences DepartmentDrexel UniversityPhiladelphiaUSA

Personalised recommendations