Diagnosis of Osteosarcopenia – Biochemistry and Pathology

  • Barbara Obermayer-Pietsch
  • Markus HerrmannEmail author


Sarcopenia and osteopenia/osteoporosis are two frequent conditions that often coexist amongst frail, older adults. Individuals affected from both conditions at the same time harbor a risk for adverse outcome that is substantially higher than the additive risk related to each of the two diseases. This observation lead to the description of a new entity called osteosarcopenia. Affected patients benefit from an appropriate care plan, which is based on a correct diagnosis. Establishment of the diagnosis includes the assessment of clinical risk factors and the determination of bone and muscle mass. The latter two are measured by dual-energy X-ray absorptiometry (DXA). Additional aspects in the workup of patients with osteosarcopenia include the biochemical assessment of bone and muscle metabolism and the exploration of secondary causes, such as hyperparathyroidism, vitamin D deficiency or malnutrition. Considering that these conditions can potentially be treated, patients benefit substantially from early diagnosis and treatment. Guidelines that provide specific recommendations for biochemical tests during the workup of osteosarcopenic patients are currently lacking. Therefore, the following pages provide a rather subjective overview based on the practical experience of the authors and existing separate guidelines for osteoporosis and sarcopenia. Furthermore, histomorphometric analyses and genetic tests will be addressed.


Osteosarcopenia Hyperparathyroidism Vitamin D deficiency Myokines Cytokine Bone morphogenetic proteins Homocysteine Histomorphometry Genetics Guidelines Glucocorticoids Muscular dystrophy Mutations Calcium 


  1. Adams JS, Hewison M (2012) Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch Biochem Biophys 523(1):95–102. Available from: Scholar
  2. Adams JS, Rafison B, Witzel S, Reyes RE, Shieh A, Chun R et al (2014) Regulation of the extrarenal CYP27B1-hydroxylase. J Steroid Biochem Mol Biol 144(PART A):22–27. Available from: Scholar
  3. Adler R, Curtis J, K. Saag RW. (2008) Glucocorticoid-induced osteoporosis. In: Osteoporosis. Elsevier Academic Press, Burlington, p 1941Google Scholar
  4. Adragao T, Ferreira A, Frazao JM, Papoila AL, Pinto I, Monier-Faugere MC et al (2017) Higher mineralized bone volume is associated with a lower plain X-Ray vascular calcification score in hemodialysis patients. PLoS One 12(7):1–14CrossRefGoogle Scholar
  5. Agmon-Levin N, Theodor E, Segal RM, Shoenfeld Y (2013) Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol 45(2):256–266. Available from: Scholar
  6. Ahmadi-Abhari S, Luben RN, Wareham NJ, Khaw KT (2013) C-reactive protein and fracture risk: European prospective investigation into cancer norfolk study. Bone. 56(1):67–72. Available from: Scholar
  7. Allanore Y, Borderie D, Lemaréchal H, Cherruau B, Ekindjian OG, Kahan A (2003) Correlation of serum collagen I carboxyterminal telopeptide concentrations with cutaneous and pulmonary involvement in systemic sclerosis. J Rheumatol 30(1):68–73. Available from: Scholar
  8. Arasu A, Cawthon PM, Lui L-Y, Do TP, Arora PS, Cauley JA et al (2012) Serum sclerostin and risk of hip fracture in older Caucasian women. J Clin Endocrinol Metab 97(6):2027–2032. Available from: Scholar
  9. Ates Bulut E, Soysal P, Aydin AE, Dokuzlar O, Kocyigit SE, Isik AT (2017) Vitamin B12 deficiency might be related to sarcopenia in older adults. Exp Gerontol 95:136–140. Available from: Scholar
  10. Ballak SB, Degens H, de Haan A, Jaspers RT (2014) Aging related changes in determinants of muscle force generating capacity: a comparison of muscle aging in men and male rodents. Ageing Res Rev 14(1):43–55. Available from: Scholar
  11. Bano G, Trevisan C, Carraro S, Solmi M, Luchini C, Stubbs B et al (2017) Inflammation and sarcopenia: a systematic review and meta-analysis. Maturitas 96:10–15. Available from: Scholar
  12. Barbour KE, Lui L-Y, Ensrud KE, Hillier TA, LeBlanc ES, Ing SW et al (2014) Inflammatory markers and risk of hip fracture in older white women: the study of osteoporotic fractures. J Bone Miner Res 29(9):2057–2064. Available from: Scholar
  13. Barker ME, McCloskey E, Saha S, Gossiel F, Charlesworth D, Powers HJ et al (2005) Serum retinoids and β-carotene as predictors of hip and other fractures in elderly women. J Bone Miner Res 20(6):913–920. Available from: Scholar
  14. Basaria S, Bhasin S (2012) Clinical implications of basic research targeting the skeletal muscle – metabolism axis in prostate-cancer therapy. N Engl J Med Clin 2012:2012–2014Google Scholar
  15. Batsis JA, Villareal DT (2018) Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. Springer US 14(9):513–537. Scholar
  16. Bauer DC, Garnero P, Bilezikian JP, Greenspan SL, Ensrud KE, Rosen CJ et al (2006) Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 91(4):1370–1375. Available from: Scholar
  17. Baumgartner RN, Koehler KM, Romero L, Garry PJ (1996) Serum albumin is associated with skeletal muscle in elderly men and women. Am J Clin Nutr 64(4):552–558. Available from: Scholar
  18. Bellettato CM, Hubert L, Scarpa M, Wangler MF (2018) Inborn errors of metabolism involving complex molecules: lysosomal and peroxisomal storage diseases. Pediatr Clin North Am. Elsevier Inc 65(2):353–373. Available from: Scholar
  19. Berglundh S, Malmgren L, Luthman H, McGuigan F, Åkesson K (2014) C-reactive protein, bone loss, fracture, and mortality in elderly women: a longitudinal study in the OPRA cohort. Osteoporos Int 26(2):727–735. Available from: Scholar
  20. Bhattoa HP, Konstantynowicz J, Laszcz N, Wojcik M, Pludowski P (2017) Vitamin D: musculoskeletal health. Rev Endocr Metab Disord 18(3):363–371. Available from: Scholar
  21. Biasin V, Obermayer-Pietsch B (2018) Sclerostin, bone morphogenetic protein, Wnt and the lung: a potential role beyond bone metabolism? J Lab Precis Med 3:102–102. Available from: Scholar
  22. Bieglmayer C, Kudlacek S (2009) The bone marker plot: an innovative method to assess bone turnover in women. Eur J Clin Invest 39(3):230–238PubMedCrossRefGoogle Scholar
  23. Bieglmayer C, Dimai HP, Gasser RW, Kudlacek S, Obermayer-Pietsch B, Woloszczuk W et al (2012) Biomarkers of bone turnover in diagnosis and therapy of osteoporosis: a consensus advice from an Austrian working group. Wiener Medizinische Wochenschrift 162(21–22):464–477. Available from: Scholar
  24. Bilezikian JP, Potts JT, El-Hajj Fuleihan G, Kleerekoper M, Neer R, Peacock M et al (2002) Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. J Clin Endocrinol Metab 87(12):5353–5361. Available from: Scholar
  25. Bilezikian JP, Bandeira L, Khan A, Cusano NE (2018) Hyperparathyroidism. Lancet 391(10116):168–178. Available from: Scholar
  26. Binkley N, Buehring B (2009) Beyond FRAX®: it’s time to consider “Sarco-Osteopenia.”. J Clin Densitom 12(4):413–416. Available from: Scholar
  27. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356(18):1809–1822. Available from: Scholar
  28. Blouin S, Thaler HW, Korninger C, Schmid R, Hofstaetter JG, Zoehrer R et al (2009) Bone matrix quality and plasma homocysteine levels. Bone 44(5):959–964. Available from: Scholar
  29. Blumsohn A, Marin F, Nickelsen T, Brixen K, Sigurdsson G, González de la Vera J et al (2011) Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide. Osteoporos Int 22(6):1935–1946. Available from: Scholar
  30. Bonafe L, Cormier-Daire V, Hall C, Lachman R, Mortier G, Mundlos S et al (2015) Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet Part A 167(12):2869–2892CrossRefGoogle Scholar
  31. Bonewald LF (2007) Osteocyte messages from a bony tomb. Cell Metab 5(6):410–411. Available from: Scholar
  32. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC et al (2012) A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382):463–468. Available from: Scholar
  33. Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473(2):139–146. Available from: Scholar
  34. Briot K, Geusens P, Em Bultink I, Lems WF, Roux C (2017) Inflammatory diseases and bone fragility. Osteoporos Int 28(12):3301–3314. Available from: Scholar
  35. Brown JE, Cook RJ, Major P, Lipton A, Saad F, Smith M et al (2005) Bone turnover markers as predictors of skeketal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst 97(1):59–69. Available from: Scholar
  36. Buckley L, Humphrey MB (2018) Glucocorticoid-induced osteoporosis. Solomon CG, editor. N Engl J Med 379(26):2547–2556. Available from: Scholar
  37. Burch J, Rice S, Yang H, Neilson A, Stirk L, Francis R et al (2014) Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups. Health Technol Assess. 18(11):1–180. Available from: Scholar
  38. Burke CW (1969) The effect of oral contraceptives on cortisol metabolism. J Clin Pathol 23(Suppl(3)):11–18CrossRefGoogle Scholar
  39. Byerly S, Benjamin E, Biswas S, Cho J, Wang E, Wong MD et al (2017) Peak creatinine kinase level is a key adjunct in the evaluation of critically ill trauma patients. Am J Surg 214(2):201–206. Available from: Scholar
  40. Cai B, Li X, Wang Y, Liu Y, Yang F, Chen H et al (2013) Apoptosis of bone marrow mesenchymal stem cells caused by homocysteine via activating JNK signal. Beltrami AP, editor. PLoS One 8(5):e63561. Available from: Scholar
  41. Cai C, Anthony DC, Pytel P (2018) A pattern-based approach to the interpretation of skeletal muscle biopsies. Mod Pathol. Springer US. Available from: Scholar
  42. Carpenter TO, Insogna KL, Zhang JH, Ellis B, Nieman S, Simpson C et al (2010) Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia: circadian variance, effects of treatment, and relationship to parathyroid status. J Clin Endocrinol Metab 95(11):E352–E357. Available from: Scholar
  43. Cauley JA, Barbour KE, Harrison SL, Cloonan YK, Danielson ME, Ensrud KE et al (2016) Inflammatory markers and the risk of hip and vertebral fractures in men: the osteoporotic fractures in men (MrOS). J Bone Miner Res 31(12):2129–2138. Available from: Scholar
  44. Cetani F, Pardi E, Borsari S, Marcocci C (2011) Molecular pathogenesis of primary hyperparathyroidism. J Endocrinol Invest 34(7 Suppl):35–39. Available from: Scholar
  45. Chapurlat RD, Confavreux CB (2016) Novel biological markers of bone: from bone metabolism to bone physiologya. Rheumatol (United Kingdom) 55(10):1714–1725Google Scholar
  46. Chen MJ, Han DS, Yang JH, Yang YS, Ho HN, Yang WS (2012) Myostatin and its association with abdominal obesity, androgen and follistatin levels in women with polycystic ovary syndrome. Hum Reprod 27(8):2476–2483PubMedCrossRefPubMedCentralGoogle Scholar
  47. Chen GD, Zhu YY, Cao Y, Liu J, Shi WQ, Liu ZM et al (2015) Association of dietary consumption and serum levels of vitamin A and β-carotene with bone mineral density in Chinese adults. Bone 79:110–115. Available from: Scholar
  48. Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW (2003) De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxylase. J Biol Chem 278(39):38084–38093. Available from: Scholar
  49. Clowes JA, Peel NFA, Eastell R (2004) The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89(3):1117–1123. Available from: Scholar
  50. Coin A, Perissinotto E, Enzi G, Zamboni M, Inelmen EM, Frigo AC et al (2008) Predictors of low bone mineral density in the elderly: the role of dietary intake, nutritional status and sarcopenia. Eur J Clin Nutr 62(6):802–809. Available from: Scholar
  51. Costa-Guda J, Arnold A (2017) Hyperparathyroidism. Genet Bone Biol Skelet Dis Second Ed 391(10116):599–615. Available from: Scholar
  52. D’Adamo CR, Shardell MD, Hicks GE, Orwig DL, Hochberg MC, Semba RD et al (2011) Serum vitamin E concentrations among highly functioning hip fracture patients are higher than in nonfracture controls. Nutr Res 31(3):205–214. Available from: Scholar
  53. Dahl K, Ahmed LA, Joakimsen RM, Jørgensen L, Eggen AE, Eriksen EF et al (2015) High-sensitivity C-reactive protein is an independent risk factor for non-vertebral fractures in women and men: the Tromsø Study. Bone 72:65–70. Available from: Scholar
  54. Dai Z, Wang R, Ang LW, Yuan JM, Koh WP (2013) Dietary B vitamin intake and risk of hip fracture: the Singapore Chinese Health Study. Osteoporos Int 24(7):2049–2059. Available from: Scholar
  55. Dai X, Du K, Li Z, Sun H, Yang Y, Zhang X et al (2015) Highly efficient hydrogen evolution catalysis by MoS2-MoN/carbonitride composites derived from tetrathiomolybdate/polymer hybrids. Chem Eng Sci 134(3):572–580. Available from: Scholar
  56. De Jonge EAL, Kiefte-De Jong JC, Campos-Obando N, Booij L, Franco OH, Hofman A et al (2015) Dietary Vitamin A intake and bone health in the elderly: the Rotterdam Study. Eur J Clin Nutr 69(12):1360–1368. Available from: Scholar
  57. Demers LM, Costa L, Chinchilli VM, Gaydos L, Curley E, Lipton A (1995) Biochemical markers of bone turnover in patients with metastatic bone disease. Clin Chem 41(10):1489–1494. Available from: Scholar
  58. Demontis F, Piccirillo R, Goldberg AL, Perrimon N (2013) The influence of skeletal muscle on systemic aging and lifespan. Aging Cell 12(6):943–949PubMedCrossRefGoogle Scholar
  59. Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H et al (2013) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28(1):2–17. Available from: Scholar
  60. Dhonukshe-Rutten RAM, Pluijm SMF, De Groot LCPGM, Lips P, Smit JH, Van Staveren WA (2005) Homocysteine and vitamin B12status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res 20(6):921–929. Available from: Scholar
  61. Di Nisio A, De Toni L, Rocca MS, Ghezzi M, Selice R, Taglialavoro G et al (2018) negative association between sclerostin and INSL3 in isolated human osteocytes and in klinefelter syndrome: new hints for testis-bone crosstalk. J Clin Endocrinol Metab 103(5):2033–2041PubMedCrossRefGoogle Scholar
  62. Dickerson RN, Alexander KH, Minard G, Croce MA, Brown RO (2004) Accuracy of methods to estimate ionized and “corrected” serum calcium concentrations in critically ill multiple trauma patients receiving specialized nutrition support. J Parenter Enter Nutr 28(3):133–141. Available from: Scholar
  63. Durosier-Izart C, Biver E, Merminod F, Van Rietbergen B, Chevalley T, Herrmann FR et al (2017) Peripheral skeleton bone strength is positively correlated with total and dairy protein intakes in healthy postmenopausal women. Am J Clin Nutr 105(2):513–525. Available from: Scholar
  64. Ekblom B (2017) The muscle biopsy technique. Historical and methodological considerations. Scand J Med Sci Sport 27(5):458–461CrossRefGoogle Scholar
  65. Emery AE (2002) The muscular dystrophies. Lancet 359(9307):687–695. Available from: Scholar
  66. Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE et al (2012) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 44(5):491–501. Available from: Scholar
  67. Fahrleitner-Pammer A, Herberth J, Browning SR, Obermayer-Pietsch B, Wirnsberger G, Holzer H et al (2008) Bone markers predict cardiovascular events in chronic kidney disease∗. J Bone Miner Res 23(11):1850–1858. Available from: Scholar
  68. Fall PM, Kennedy D, Smith JA, Seibel MJ, Raisz LG (2000) Comparison of serum and urine assays for biochemical markers of bone resorption in postmenopausal women with and without hormone replacement therapy and in men. Osteoporos Int 11(6):481–485. Available from: Scholar
  69. Farrell C-J, Herrmann M (2013) Determination of vitamin D and its metabolites. Best Pract Res Clin Endocrinol Metab 27(5):675–688. Available from: Scholar
  70. Farrell CJL, Martin S, McWhinney B, Straub I, Williams P, Herrmann M (2012a) State-of-the-art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods. Clin Chem 58(3):531–542. Available from: Scholar
  71. Farrell C, Soldo J, Williams P, Herrmann M (2012b) 25-hydroxyvitamin D testing: challenging the performance of current automated immunoassays. Clin Chem Lab Med 50(11):1953–1963. Available from: Scholar
  72. Ferrari R, Caram LMO, Faganello MM, Sanchez FF, Tanni SE, Godoy I (2015) Relation between systemic inflammatory markers, peripheral muscle mass, and strength in limb muscles in stable COPD patients. Int J COPD 10(1):1553–1558. Available from:
  73. Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A et al (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142(2):296–308. Available from: Scholar
  74. Findlay DM, Atkins GJ (2011) Relationship between serum RANKL and RANKL in bone. Osteoporos Int 22(10):2597–2602. Available from: Scholar
  75. Finigan J, Greenfield DM, Blumsohn A, Hannon RA, Peel NF, Jiang G et al (2008) Risk factors for vertebral and nonvertebral fracture over 10 years: a population-based study in women. J Bone Miner Res 23(1):75–85. Available from: Scholar
  76. Fink HA, Vo TN, Langsetmo L, Barzilay JI, Cauley JA, Schousboe JT et al (2017) Association of increased urinary albumin with risk of incident clinical fracture and rate of hip bone loss: the osteoporotic fractures in men study. J Bone Miner Res 32(5):1090–1099. Available from: Scholar
  77. Fisher A, Srikusalanukul W, Fisher L, Smith PN (2017) Lower serum P1NnP/βCTX ratio and hypoalbuminemia are independently associated with osteoporotic nonvertebral fractures in older adults. Clin Interv Aging 12:1131–1140. Available from: Scholar
  78. Foessl I, Kotzbeck P, Obermayer-Pietsch B (2019) miRNAs as novel biomarkers for bone related diseases. J Lab Precis Med 4:2–2. Available from: Scholar
  79. Forman DT, Lorenzo L (1991) Ionized calcium its significance and clinical usefulness-Forman1991p1629.pdf. Ann Clin Lab Sci 21(5):297–304. Available from: Scholar
  80. Fung TT, Feskanich D (2015) Dietary patterns and risk of hip fractures in postmenopausal women and men over 50 years. Osteoporos Int 26(6):1825–1830. Available from: Scholar
  81. Garcia Lopez M, Baron JA, Omsland TK, Søgaard AJ, Meyer HE (2018) Homocysteine-lowering treatment and the risk of fracture: secondary analysis of a randomized controlled trial and an updated meta-analysis. JBMR Plus 2(5):295–303. Available from: Scholar
  82. Gardeitchik T, Wyckmans J, Morava E (2018) Complex phenotypes in inborn errors of metabolism: overlapping presentations in congenital disorders of glycosylation and mitochondrial disorders. Pediatr Clin North Am 65(2):375–388PubMedCrossRefGoogle Scholar
  83. Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C et al (1996) Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 11(10):1531–1538. Available from: Scholar
  84. Garnero P, Ferreras M, Karsdal MA, Nicamhlaoibh R, Risteli J, Borel O et al (2003) The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res 18(5):859–867. Available from: Scholar
  85. Garnero P, Sornay-Rendu E, Munoz F, Borel O, Chapurlat RD (2013) Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int 24(2):489–494. Available from: Scholar
  86. Gerdhem P, Åkesson K (2007) Trauma Rates of fracture in participants and non- participants in the Osteoporosis Prospective Risk Assessment Study. J bone Jt Surg Br Vol 89(12):1627–1631. Available from: Scholar
  87. Gerdhem P, Ivaska KK, Alatalo SL, Halleen JM, Hellman J, Isaksson A et al (2004) Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res 19(3):386–393. Available from: Scholar
  88. Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ et al (2006) Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 98(7):451–459. Available from: Scholar
  89. Giudice J, Taylor JM (2017) Muscle as a paracrine and endocrine organ. Curr Opin Pharmacol 34:49–55. Available from: Scholar
  90. Giuliani S, Barbieri V, Di Pierro AM, Rossi F, Widmann T, Lucchiari M, et al (2018) LC–MS/MS based 25(OH)D status in a large Southern European outpatient cohort: gender- and age-specific differences. Eur J Nutr 7. Available from:
  91. Gjesdal CG, Vollset SE, Ueland PM, Refsum H, Drevon CA, Gjessing HK et al (2006) Plasma total homocysteine level and bone mineral density: the Hordaland Homocysteine Study. Arch Intern Med 166(1):88–94. Available from: Scholar
  92. Gjesdal CG, Vollset SE, Ueland PM, Refsum H, Meyer HE, Tell GS (2007) Plasma homocysteine, folate, and vitamin B12 and the risk of hip fracture: the hordaland homocysteine study. J Bone Miner Res 22(5):747–756. Available from: Scholar
  93. Glassock RJ, Rule AD (2016) Aging and the kidneys: anatomy, physiology and consequences for defining chronic kidney disease. Nephron 134(1):25–29. Available from: Scholar
  94. Gossiel F, Scott JR, Paggiosi MA, Naylor KE, McCloskey EV, Peel NFA et al (2018) Effect of teriparatide treatment on circulating periostin and its relationship to regulators of bone formation and BMD in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 103(4):1302–1309PubMedPubMedCentralCrossRefGoogle Scholar
  95. Granic A, Davies K, Martin-Ruiz C, Jagger C, Kirkwood TBL, von Zglinicki T et al (2017) Grip strength and inflammatory biomarker profiles in very old adults. Age Ageing 46(6):976–982. Available from: Scholar
  96. Green TJ, McMahon JA, Skeaff CM, Williams SM, Whiting SJ (2007) Lowering homocysteine with B vitamins has no effect on blood pressure in older adults. Am J Clin Nutr 137(5):1183–1187. Available from: Scholar
  97. Greenblatt MB, Tsai JN, Wein MN (2017) Bone turnover markers in the diagnosis and monitoring of metabolic bone disease. Clin Chem 63(2):464–474. Available from: Scholar
  98. Gundberg CM, Markowitz ME, Mizruchi M, Rosen JF (1985) Osteocalcin in human serum: a circadian rhythm. J Clin Endocrinol Metab 60(4):736–739. Available from: Scholar
  99. Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänänen HK (2006) Tartrate-resistant acid phosphates 5b (TRACP 5b) as a marker of bone resorption. Clin Lab 52(9–10):499–509. Available from: Scholar
  100. Hassan EB, Duque G (2017) Osteosarcopenia: a new geriatric syndrome. Aust Fam Physician 46(11):849–853. Available from: Scholar
  101. Hassan MQ, Tye CE, Stein GS, Lian JB (2015) Non-coding RNAs: epigenetic regulators of bone development and homeostasis. Bone 81:746–756. Available from: Scholar
  102. Hede MS, Salimova E, Piszczek A, Perlas E, Winn N, Nastasi T et al (2012) E-peptides control bioavailability of IGF-1. PLoS One 7(12):e51152PubMedPubMedCentralCrossRefGoogle Scholar
  103. Hendy GN, Cole DEC (2013) Genetic defects associated with familial and sporadic hyperparathyroidism. Endocrine Tumor Syndromes Their Genetics 41:149–156. Available from: Scholar
  104. Henneicke H, Herrmann M, Kalak R, Brennan-Speranza TC, Heinevetter U, Bertollo N et al (2011) Corticosterone selectively targets endo-cortical surfaces by an osteoblast-dependent mechanism. Bone 49(4):733–742. Available from: Scholar
  105. Henriksen DB, Alexandersen P, Bjarnason NH, Vilsbøll T, Hartmann B, Henriksen EE et al (2003) Role of gastrointestinal hormones in postprandial reduction of bone resorption. J Bone Miner Res 18(12):2180–2189. Available from: Scholar
  106. Henriksen K, Tanko LB, Qvist P, Delmas PD, Christiansen C, Karsdal MA (2007) Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases. Osteoporos Int 18(5):681–685. Available from: Scholar
  107. Herrmann M, Seibel M (2008) The amino- and carboxyterminal cross-linked telopeptides of collagen type I, NTX-I and CTX-I: a comparative review. Clin Chim Acta 393(2):57–75. Available from: Scholar
  108. Herrmann M, Widmann T, Colaianni G, Colucci S, Zallone A, Herrmann W (2005) Increased osteoclast activity in the presence of increased homocysteine concentrations. Clin Chem 51(12):2348–2353. Available from: Scholar
  109. Herrmann M, Peter Schmidt J, Umanskaya N, Wagner A, Taban-Shomal O, Widmann T et al (2007a) The role of hyperhomocysteinemia as well as folate, vitamin B6and B12deficiencies in osteoporosis – a systematic review. Clin Chem Lab Med 45(12):1621–1632. Available from: Scholar
  110. Herrmann M, Wildemann B, Claes L, Klohs S, Ohnmacht M, Taban-Shomal O et al (2007b) Experimental hyperhomocysteinemia reduces bone quality in rats. Clin Chem. 53(8):1455–1461. Available from: Scholar
  111. Herrmann M, Schmidt J, Umanskaya N, Colaianni G, Al Marrawi F, Widmann T et al (2007c) Stimulation of osteoclast activity by low B-vitamin concentrations. Bone 41(4):584–591. Available from: Scholar
  112. Herrmann M, Umanskaya N, Wildemann B, Colaianni G, Widmann T, Zallone A et al (2008) Stimulation of osteoblast activity by homocysteine. J Cell Mol Med 12(4):1205–1210. Available from: Scholar
  113. Herrmann M, Tami A, Wildemann B, Wolny M, Wagner A, Schorr H et al (2009a) Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone. Bone 44(3):467–475. Available from: Scholar
  114. Herrmann M, Wildemann B, Wagner A, Wolny M, Schorr H, Taban-Shomal O et al (2009b) Experimental Folate and Vitamin B12Deficiency Does Not Alter bone quality in rats. J Bone Miner Res 24(4):589–596. Available from: Scholar
  115. Herrmann M, Sullivan DR, Veillard AS, McCorquodale T, Straub IR, Scott R et al (2015) Serum 25-Hydroxyvitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes. Diabetes Care 38(3):521–528. Available from: Scholar
  116. Hirschfeld HP, Kinsella R, Duque G (2017) Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int 28(10):2781–2790. Available from: Scholar
  117. Holick MF, Gordon CM (2011) The Hormone Foundation’s: patient guide to vitamin D deficiency. Holick MF, Gordon CM, editors. J Clin Endocrinol Metab 96(7):1–2. Available from: Scholar
  118. Holick MF, Chen TC, Lu Z, Sauter E (2007) Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res 22(SUPPL. 2):V28–V33. Available from: Scholar
  119. Holvik K, Gjesdal CG, Tell GS, Grimnes G, Schei B, Apalset EM et al (2014) Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture. A NOREPOS study. Osteoporos Int 25(11):2545–2554. Available from: Scholar
  120. Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB et al (2008) Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) study. Am J Clin Nutr 87(1):150–155. Available from: Scholar
  121. Hunt A, Harrington D, Robinson S (2014) Vitamin B12 deficiency. BMJ 349(sep04 1):g5226. Available from: Scholar
  122. Igarashi Y, Lee MY, Matsuzaki S (2002) Acid phosphatases as markers of bone metabolism. J Chromatogr B Anal Technol Biomed Life Sci 781(1–2):345–358. Available from: Scholar
  123. Inzitari M, Doets E, Bartali B, Benetou V, Di Bari M, Visser M et al (2011) Nutrition in the age-related disablement process. J Nutr Health Aging 15(8):599–604. Available from: Scholar
  124. Isanejad M, Sirola J, Mursu J, Kröger H, Tuppurainen M, Erkkilä AT (2017) Association of protein intake with bone mineral density and bone mineral content among elderly women: the OSTPRE fracture prevention study. J Nutr Heal Aging 21(6):622–630. Available from: Scholar
  125. Ivaska KK, Hentunen TA, Vääräniemi J, Ylipahkala H, Pettersson K, Väänänen HK (2004) Release of intact and fragmented osteocalcin molecules from bone matrix during bone resorption in vitro. J Biol Chem 279(18):18361–18369. Available from: Scholar
  126. Janson JJ, Galarza CR, Murúa A, Quintana I, Przygoda PA, Waisman G et al (2002) Prevalence of hyperhomocysteinemia in an elderly population. Am J Hypertens 15(5):394–397. Available from: Scholar
  127. Kalpakcioglu BB, Engelke K, Genant HK (2011) Advanced imaging assessment of bone fragility in glucocorticoid-induced osteoporosis. Bone. Elsevier Inc 48(6):1221–1231. Scholar
  128. Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S et al (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22(1):187–194PubMedCrossRefGoogle Scholar
  129. Karsenty G, Olson EN (2016) Bone and muscle endocrine functions: unexpected paradigms of inter-organ communication. Cell 164(6):1248–1256. Available from: Scholar
  130. Khairallah P, Nickolas TL (2018) Updates in CKD-associated osteoporosis. Curr Osteoporos Rep 16(6):712–723. Available from: Scholar
  131. Khan AA, Hanley DA, Rizzoli R, Bollerslev J, Young JEM, Rejnmark L et al (2017) Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus. Osteoporos Int 28(1):1–19. Available from: Scholar
  132. Khoury N, Carmichael KA (2011a) Evaluation and therapy of hypercalcemia. Mo Med 108(2):99–103. Available from: Scholar
  133. Khoury N, Carmichael KA (2011b) Evaluation and therapy of hypercalcemia. Mo Med 108(2):99–103. Available from: Scholar
  134. Kim JH, Kwak MK, Ahn SH, Kim H, Cho YY, Suh S et al (2018) Alteration in skeletal muscle mass in women with subclinical hypercortisolism. Endocrine 61(1):134–143. Available from: Scholar
  135. Klappacher G, Franzen P, Haab D, Mehrabi M, Binder M, Plesch K et al (1995) Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis. Am J Cardiol 75(14):913–918. Available from: Scholar
  136. Koh LKH (2003) The diagnosis and management of hypercalcaemia. Ann Acad Med Singapore 32(1):129–139. Available from: Scholar
  137. Kubat Uzum A, Salman S, Telci A, Boztepe H, Tanakol R, Alagol F et al (2010) Effects of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women in short term. Eur J Endocrinol 163(5):825–831. Available from: Scholar
  138. Kunishige M, Kijima Y, Sakai T, Akutagawa O, Matsuo A, Nishibe A et al (2007) Transient enhancement of oxidant stress and collagen turnover in patients with acute worsening of congestive heart failure. Circ J 71(12):1893–1897. Available from: Scholar
  139. Kuro-O M (2013) Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism. Nat Rev Nephrol 9(11):650–660. Available from: Scholar
  140. Lai CH, Melli G, Chang YJ, Skolasky RL, Corse AM, Wagner KR et al (2010) Open muscle biopsy in suspected myopathy: diagnostic yield and clinical utility. Eur J Neurol 17(1):136–142PubMedCrossRefPubMedCentralGoogle Scholar
  141. Larsson L, Magnussen P (2003) Ionized calcium or corrected total calcium? J Bone Miner Res 18(8):1554–1555. Available from: Scholar
  142. Lassche S, Janssen BH, IJzermans T, Fütterer JJ, Voermans NC, Heerschap A et al (2018) MRI-guided biopsy as a tool for diagnosis and research of muscle disorders. J Neuromuscul Dis 5(3):315–319. Available from: Scholar
  143. Lee S-J, McPherron AC (2001) Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci 98(16):9306–9311. Available from: Scholar
  144. Li EK, Tam LS, Griffith JF, Zhu TY, Li TK, Li M et al (2009) High prevalence of asymptomatic vertebral fractures in Chinese women with systemic lupus erythematosus. J Rheumatol 36(8):1646–1652. Available from: Scholar
  145. Liu Y, Shi Z, Silveira A, Liu J, Sawadogo M, Yang H et al (2003a) Involvement of upstream stimulatory factors 1 and 2 in RANKL-induced transcription of tartrate-resistant acid phosphatase gene during osteoclast differentiation. J Biol Chem 278(23):20603–20611. Available from: Scholar
  146. Liu S, Guo R, Simpson LG, Xiao Z-S, Burnham CE, Quarles LD (2003b) Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX. J Biol Chem 278(39):37419–37426. Available from: Scholar
  147. Lomeo A, Bolner A (2000) Stability of several biochemical markers of bone metabolism. Clin Chem 46(8 I):1200–1202PubMedGoogle Scholar
  148. Maagensen H, Junker AE, Jørgensen NR, Gluud LL, Knop FK, Vilsbøll T (2018) Bone turnover markers in patients with nonalcoholic fatty liver disease and/or type 2 diabetes during oral glucose and isoglycemic intravenous glucose. J Clin Endocrinol Metab 103(5):2042–2049PubMedCrossRefGoogle Scholar
  149. Mace ML, Gravesen E, Nordholm A, Olgaard K, Lewin E (2018) Fibroblast growth factor (FGF) 23 regulates the plasma levels of parathyroid hormone in vivo through the FGF receptor in normocalcemia, but not in hypocalcemia. Calcif Tissue Int 102(1):85–92. Available from: Scholar
  150. McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE et al (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350(20):2042–2049. Available from: Scholar
  151. McLean RR, Jacques PF, Selhub J, Fredman L, Tucker KL, Samelson EJ et al (2008) Plasma B vitamins, homocysteine, and their relation with bone loss and hip fracture in elderly men and women. J Clin Endocrinol Metab 93(6):2206–2212. Available from: Scholar
  152. Mercuri E, Muntoni F (2013) Muscular dystrophy. Curr Opin Pediatr 25(6):701–707. Available from: Scholar
  153. Michaëlsson K, Lithell H, Vessby B, Melhus H (2003) Serum retinol levels and the risk of fracture. New Engl J Med 348(4):287–294. Available from: Scholar
  154. Michaëlsson K, Wolk A, Byberg L, Ärnlöv J, Melhus H (2014) Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies. Am J Clin Nutr 99(1):107–114. Available from: Scholar
  155. Michelsen J, Wallaschofski H, Friedrich N, Spielhagen C, Rettig R, Ittermann T et al (2013) Reference intervals for serum concentrations of three bone turnover markers for men and women. Bone 57(2):399–404. Available from: Scholar
  156. Midtby M, Magnus JH, Joakimsen RM (2001) The Troms?? Study: a population-based study on the variation in bone formation markers with age, gender, anthropometry and season in both men and women. Osteoporos Int 12(10):835–843. Available from: Scholar
  157. Miller PD (2014) Chronic kidney disease and osteoporosis: evaluation and management. Bonekey Rep 3:542. Available from: Scholar
  158. Miller WL (2017) Genetic disorders of Vitamin D biosynthesis and degradation. J Steroid Biochem Mol Biol 165(Pt A):101–108. Available from: Scholar
  159. Minetto MA, Botter A, Lanfranco F, Baldi M, Ghigo E, Arvat E (2010) Muscle fiber conduction slowing and decreased levels of circulating muscle proteins after short-term dexamethasone administration in healthy subjects. J Clin Endocrinol Metab 95(4):1663–1671. Available from: Scholar
  160. Minetto MA, Qaisar R, Agoni V, Motta G, Longa E, Miotti D et al (2015) Quantitative and qualitative adaptations of muscle fibers to glucocorticoids. Muscle Nerve 52(4):631–639. Available from: Scholar
  161. Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95(4):1991–1997. Available from: Scholar
  162. Mirza MA, Karlsson MK, Mellström D, Orwoll E, Ohlsson C, Ljunggren Ö et al (2011) Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men. J Bone Miner Res 26(4):857–864. Available from: Scholar
  163. Mitri J, Muraru MD, Pittas AG (2011) Vitamin D and type 2 diabetes: a systematic review. Eur J Clin Nutr 65(9):1005–1015. Available from: Scholar
  164. Moorthi RN, Avin KG (2017) Clinical relevance of sarcopenia in chronic kidney disease. Curr Opin Nephrol Hypertens 26(3):219–228. Available from: Scholar
  165. Mornet E (2017) Genetics of hypophosphatasia. Arch Pédiatrie 24(5):5S51–5S56. Available from: Scholar
  166. Morris MS, Jacques PF, Selhub J (2005) Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 37(2):234–242. Available from: Scholar
  167. Nakanishi M, Yoh K, Miura T, Ohasi T, Rai SK, Uchida K (2000) Development of a kinetic assay for band 5b tartrate-resistant acid phosphatase activity in serum. Clin Chem 46(4):469–473. Available from: Scholar
  168. Napoli N, Strollo R, Defeudis G, Leto G, Moretti C, Zampetti S et al (2018) Serum sclerostin and bone turnover in latent autoimmune diabetes in adults. J Clin Endocrinol Metab 103(5):1921–1928PubMedCrossRefPubMedCentralGoogle Scholar
  169. Naylor KE, Jacques RM, Paggiosi M, Gossiel F, Peel NFA, McCloskey EV et al (2016) Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos Int 27(1):21–31. Available from: Scholar
  170. Ng TP, Aung KCY, Feng L, Scherer SC, Yap KB (2012) Homocysteine, folate, vitamin B-12, and physical function in older adults: cross-sectional findings from the Singapore longitudinal ageing study. Am J Clin Nutr 96(6):1362–1368. Available from: Scholar
  171. Obeid R, Schorr H, Eckert R, Herrmann W (2004) Vitamin B12 status in the elderly as judged by available biochemical markers. Clin Chem 50(1):238–241. Available from: Scholar
  172. Obermayer-Pietsch BM, Marin F, McCloskey EV, Hadji P, Farrerons J, Boonen S et al (2008) Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res 23(10):1591–1600. Available from: Scholar
  173. Obermayer-Pietsch B, Francic V, Haudum C, Borzan V, Schweighofer N, Ascani A et al (2018) Diabetoporosity—diabetes and the bone. J Lab Precis Med 3(1):98–98. Available from: Scholar
  174. Oei L, Campos-Obando N, Dehghan A, Oei EHG, Stolk L, Van Meurs JBJ et al (2014) Dissecting the relationship between high-sensitivity serum C-reactive protein and increased fracture risk: the Rotterdam Study. Osteoporos Int 25(4):1247–1254. Available from: Scholar
  175. Opotowsky AR, Bilezikian JP (2004) Serum vitamin A concentration and the risk of hip fracture among women 50 to 74 years old in the United States: a prospective analysis of the NHANES I follow-up study. Am J Med 117(3):169–174. Available from: Scholar
  176. Paintin J, Cooper C, Dennison E (2018) Osteosarcopenia. Br J Hosp Med. Europe PMC Funders 79(5):253–258. Available from: Scholar
  177. Parisien M, Silverberg SJ, Shane E, La Cruz LD, Lindsay R, Bilezikian JP et al (1990) The histomorphometry of bone in primary hyperparathyroidism: preservation of cancellous bone structure. J Clin Endocrinol Metab 70(4):930–938PubMedCrossRefPubMedCentralGoogle Scholar
  178. Park H-S, Kim HC, Zhang D, Yeom H, Lim S-K (2018) The novel myokine irisin: clinical implications and potential role as a biomarker for sarcopenia in postmenopausal women. In: Endocrine. Springer, Ann Arbor. Available from: Scholar
  179. Peacock M (2010) Calcium metabolism in health and disease. Clin J Am Soc Nephrol 5:S23–S30. Available from: Scholar
  180. Pedersen BK (2011) Muscles and their myokines. J Exp Biol 214(2):337–346. Available from: Scholar
  181. Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8(8):457–465. Available from: Scholar
  182. Qvist P, Christgau S, Pedersen BJ, Schlemmer A, Christiansen C (2002) Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): efects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. Bone 31(1):57–61. Available from: Scholar
  183. Rabenberg M, Scheidt-Nave C, Busch MA, Rieckmann N, Hintzpeter B, Mensink GBM (2015) Vitamin D status among adults in Germany – results from the German Health Interview and Examination Survey for Adults (DEGS1) Chronic Disease epidemiology. BMC Public Health 15(1):641. Available from: Scholar
  184. Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkensammer G, Griesmacher A et al (2007) Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J Clin Endocrinol Metab 92(2):443–449PubMedCrossRefGoogle Scholar
  185. Refsum H, Guttormsen AB, Fiskerstrand T, Ueland PM (1997) On the formation and fate of total plasma homocysteine. In: Homocysteine metabolism: from basic science to clinical medicine. Springer, Boston, pp 23–29. Available from: Scholar
  186. Rennenberg RJMW, Schurgers LJ, Kroon AA, Stehouwer CDA (2010) Arterial calcifications. J Cell Mol Med 14(9):2203–2210. Available from: Scholar
  187. Revell PA (1983) Histomorphometry of bone. J Clin Pathol 36(12):1323–1331. Available from: Scholar
  188. Reynolds TM, Marshall PD, Brain AM (1992) Hip fracture patients may be vitamin b6deficient: controlled study of serum pyridoxal-5’phosphate. Acta Orthop 63(6):635–638. Available from: Scholar
  189. Ribaya-Mercado JD, Blumberg JB (2007) Vitamin A: is it a risk factor for osteoporosis and bone fracture? Nutr Rev 65(10):425–438. Available from: Scholar
  190. Rosen CJ, Gallagher JC (2011) The 2011 IOM report on vitamin D and calcium requirements for North America: clinical implications for providers treating patients with low bone mineral density. J Clin Densitom 14(2):79–84. Available from: Scholar
  191. Sahni S, Broe KE, Tucker KL, McLean RR, Kiel DP, Cupples LA et al (2014) Association of total protein intake with bone mineral density and bone loss in men and women from the Framingham Offspring Study. Public Health Nutr 17(11):2570–2576. Available from: Scholar
  192. Saito M, Fujii K, Marumo K (2006) Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. Calcif Tissue Int 79(3):160–168. Available from: Scholar
  193. Saito K, Yokoyama T, Yoshida H, Kim H, Shimada H, Yoshida Y et al (2012) A significant relationship between plasma vitamin C concentration and physical performance among Japanese elderly women. J Gerontol – Ser A Biol Sci Med Sci 67 A(3):295–301. Available from: Scholar
  194. Sakaki T, Kagawa N, Yamamoto K, Inouye K (2005) Metabolism of vitamin D3 by cytochromes P450. Front Biosci 10:119–134. Available from: Scholar
  195. Sandri M, Lin J, Handschin C, Yang W, Arany ZP, Lecker SH et al (2006) PGC-1 protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci 103(44):16260–16265. Available from: Scholar
  196. Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K (2005) Effect of folate and mecobalamin on hip fractures in patients with stroke. JAMA 293(9):1082. Available from: Scholar
  197. Sato AY, Richardson D, Cregor M, Davis HM, Au ED, McAndrews K et al (2017) Glucocorticoids induce bone and muscle atrophy by tissue-specific mechanisms upstream of E3 ubiquitin ligases. Endocrinology 158(3):664–677. Available from: Scholar
  198. Saudubray JM, Garcia-Cazorla À (2018) Inborn errors of metabolism overview: pathophysiology, manifestations, evaluation, and management. Pediatr Clin North Am 65(2):179–208PubMedCrossRefGoogle Scholar
  199. Sayer AA, Robinson SM, Patel HP, Shavlakadze T, Cooper C, Grounds MD (2013) New horizons in the pathogenesis, diagnosis and management of sarcopenia. Age Ageing 42(2):1145–1150. Available from: Scholar
  200. Schakman O, Gilson H, Thissen JP (2008) Mechanisms of glucocorticoid-induced myopathy. J Endocrinol 197(1):1–10. Available from: Scholar
  201. Schakman O, Kalista S, Barbé C, Loumaye A, Thissen JP (2013) Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol 45(10):2163–2172. Available from: Scholar
  202. Schteingart DE, Lloyd RV, Akil H, Chandler WF, Ibarra-Perez G, Rosen SG et al (1986) Cushing’s syndrome secondary to ectopic corticotropin-releasing hormone-adrenocorticotropin secretion. J Clin Endocrinol Metab 63(3):770–775. Available from: Scholar
  203. Schuelke M, Wagner KR, Stolz LE, Hübner C, Riebel T, Kömen W et al (2004) Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 350(26):2682–2688. Available from: Scholar
  204. Schwetz V, Pieber T, Obermayer-Pietsch B (2012) Mechanisms in endocrinology: the endocrine role of the skeleton: background and clinical evidence. Eur J Endocrinol 166(6):959–967. Available from: Scholar
  205. Selhub J, Jacques PF, Rosenberg IH, Rogers G, Bowman BA, Gunter EW et al (1999) Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991–1994): population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med 131(5):331–339. Available from: Scholar
  206. Semba RD, Bartali B, Zhou J, Blaum C, Ko CW, Fried LP (2006) Low serum micronutrient concentrations predict frailty among older women living in the community. J Gerontol – Ser A Biol Sci Med Sci 61(6):594–599. Available from: Scholar
  207. Shaker JL, Deftos L (2000) Calcium and phosphate homeostasis. In: Endotext., Inc, South Dartmouth. Available from: Scholar
  208. Sherman JE (1935) The diagnosis and management of anemia. South Med J. 28(12):1112–1114. Available from: Scholar
  209. Shi WQ, Liu J, Cao Y, Zhu YY, Guan K, Chen YM (2016) Association of dietary and serum Vitamin E with bone mineral density in middle-aged and elderly Chinese adults: a cross-sectional study. Br J Nutr 115(1):113–120. Available from: Scholar
  210. Shieh A, Han W, Ishii S, Greendale GA, Crandall CJ, Karlamangla AS (2016) Quantifying the balance between total bone formation and total bone resorption: an index of net bone formation. J Clin Endocrinol Metab 101(7):2802–2809. Available from: Scholar
  211. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y et al (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19(3):429–435. Available from: Scholar
  212. Silva BC, Cusano NE, Bilezikian JP (2018) Primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab 32(5):593–607. Available from: Scholar
  213. Singh R, Braga M, Reddy ST, Lee SJ, Parveen M, Grijalva V et al (2017) Follistatin targets distinct pathways to promote brown adipocyte characteristics in brown and white adipose tissues. Endocrinology 158(5):1217–1230PubMedPubMedCentralCrossRefGoogle Scholar
  214. Škovierová H, Vidomanová E, Mahmood S, Sopková J, Drgová A, Červeňová T et al (2016) The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int J Mol Sci. Multidisciplinary Digital Publishing Institute 17(10):1733. Available from: Scholar
  215. Snyder CK, Lapidus JA, Cawthon PM, Dam TTL, Sakai LY, Marshall LM (2012) Serum albumin in relation to change in muscle mass, muscle strength, and muscle power in older men. J Am Geriatr Soc 60(9):1663–1672. Available from: Scholar
  216. Song B, Li X, Zhou Q, Yang X, Jiang Y, Wang A (2018) Application of bone turnover markers PICP and β-CTx in the diagnosis and treatment of breast cancer with bone metastases. Clin Lab 64(1–2):11–16PubMedGoogle Scholar
  217. Sowers MFR, Zheng H, Greendale GA, Neer RM, Cauley JA, Ellis J et al (2013) Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity. J Clin Endocrinol Metab 98(7):2854–2863. Available from: Scholar
  218. Sprague SM, Bellorin-Font E, Jorgetti V, Carvalho AB, Malluche HH, Ferreira A et al (2016) Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis. Am J Kidney Dis 67(4):559–566PubMedCrossRefGoogle Scholar
  219. Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes J et al (2003) DACH-LIGA homocystein (German, Austrian and Swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med 41(11):1392–1403. Available from: Scholar
  220. Stankevičius A, Garnaga G (2014) Oil pollution in waters of Lithuania. Handb Environ Chem 27(4):101–124. Available from: Scholar
  221. Steinberg J, Brooks RA, Southam L, Bhatnagar S, Roumeliotis TI, Hatzikotoulas K et al (2018) Widespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis. Rheumatol (United Kingdom) 57(8):1481–1489Google Scholar
  222. Stone KL, Lui LY, Christen WG, Troen AM, Bauer DC, Kado D et al (2017) Effect of combination folic acid, vitamin B6, and vitamin B12 supplementation on fracture risk in women: a randomized, controlled trial. J Bone Miner Res 32(12):2331–2338. Available from: Scholar
  223. Stuss M, Rieske P, Cegłowska A, Stêpień-Kłos W, Liberski PP, Brzeziańska E et al (2013) Assessment of OPG/RANK/RANKL gene expression levels in peripheral blood mononuclear cells (PBMC) after treatment with strontium ranelate and ibandronate in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab 98(5):E1007–E1011. Available from: Scholar
  224. Sullivan TR, Duque G, Keech AC, Herrmann M (2013) An old friend in a new light: the role of osteocalcin in energy metabolism. Cardiovasc Ther 31(2):65–75. Available from: Scholar
  225. Taylor AF, Saunders MM, Shingle DL, Cimbala JM, Zhou Z, Donahue HJ (2007) Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions. Am J Physiol Physiol 292(1):C545–C552. Available from: Scholar
  226. ter Borg S, Verlaan S, Hemsworth J, Mijnarends DM, Schols JMGA, Luiking YC et al (2015) Micronutrient intakes and potential inadequacies of community-dwelling older adults: a systematic review. Br J Nutr 113(08):1195–1206. Available from: Scholar
  227. Thaler R, Spitzer S, Rumpler M, Fratzl-Zelman N, Klaushofer K, Paschalis EP et al (2010) Differential effects of homocysteine and beta aminopropionitrile on preosteoblastic MC3T3-E1 cells. Bone 46(3):703–709. Available from: Scholar
  228. Thaler R, Agsten M, Spitzer S, Paschalis EP, Karlic H, Klaushofer K et al (2011) Homocysteine suppresses the expression of the collagen cross-linker lysyl oxidase involving IL-6, Fli1, and epigenetic DNA methylation. J Biol Chem 286(7):5578–5588. Available from: Scholar
  229. Thiele S, Rauner M, Goes P (2018) Recent advances in periodontitis, a prototypic osteo-immunological disease. J Lab Precis Med 3:101–101. Available from: Scholar
  230. Tohma H, El-Shafey AF, Croft K, Shavlakadze T, Grounds MD, Arthur PG (2014) Protein thiol oxidation does not change in skeletal muscles of aging female mice. Biogerontology 15(1):87–98. Available from: Scholar
  231. Torbergsen AC, Watne LO, Wyller TB, Frihagen F, Strømsøe K, Bøhmer T et al (2017) Micronutrients and the risk of hip fracture: case–control study. Clin Nutr 36(2):438–443. Available from: Scholar
  232. Tsai KS, Pan WH, Hsu SHJ, Cheng WC, Chen CK, Chieng PU et al (1996) Sexual differences in bone markers and bone mineral density of normal Chinese. Calcif Tissue Int 59(6):454–460. Available from: Scholar
  233. Tuck SP, Layfield R, Walker J, Mekkayil B, Francis R (2017) Adult Paget’s disease of bone: a review. Rheumatol (United Kingdom) 56(12):2050–2059Google Scholar
  234. Tuckey RC, Cheng CYS, Slominski AT (2018) The serum vitamin D metabolome: what we know and what is still to discover. J Steroid Biochem Mol Biol. Available from:
  235. Turner JJO (2017) Hypercalcaemia – presentation and management. Clin Med J R Coll Physicians London 17(3):270–273. Available from: Scholar
  236. Tyagi N, Vacek TP, Fleming JT, Vacek JC, Tyagi SC (2011) Hyperhomocysteinemia decreases bone blood flow. Vasc Health Risk Manag 7(1):31–35. Available from: Scholar
  237. Ulbing M, Kirsch AH, Leber B, Lemesch S, Münzker J, Schweighofer N et al (2017) MicroRNAs 223-3p and 93-5p in patients with chronic kidney disease before and after renal transplantation. Bone 95:115–123. Available from: Scholar
  238. Valcour A, Blocki F, Hawkins DM, Rao SD (2012) No Title 97(11). Available from:
  239. van Dijk M, Dijk FJ, Bunschoten A, van Dartel DAM, van Norren K, Walrand S et al (2016) Improved muscle function and quality after diet intervention with leucine-enriched whey and antioxidants in antioxidant deficient aged mice. Oncotarget 5:7(14). Available from: Scholar
  240. van Dronkelaar C, van Velzen A, Abdelrazek M, van der Steen A, Weijs PJM, Tieland M (2018) Minerals and sarcopenia; the role of calcium, iron, magnesium, phosphorus, potassium, selenium, sodium, and zinc on muscle mass, muscle strength, and physical performance in older adults: a systematic review. J Am Med Dir Assoc 19(1):6–11.e3. Available from: Scholar
  241. van Meurs JBJ, Dhonukshe-Rutten RAM, Pluijm SMF, van der Klift M, de Jonge R, Lindemans J et al (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 350(20):2033–2041. Available from: Scholar
  242. van Wijngaarden JP, Doets EL, Szczecińska A, Souverein OW, Duffy ME, Dullemeijer C et al (2013) Vitamin B12, folate, homocysteine, and bone health in adults and elderly people: a systematic review with meta-analyses. J Nutr Metab. 2013:486186. Available from: Scholar
  243. Van Wijngaarden JP, Swart KMA, Enneman AW, Dhonukshe-Rutten RAM, Van Dijk SC, Ham AC et al (2014) Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial. Am J Clin Nutr 100(6):1578–1586. Available from: Scholar
  244. Vanderschueren D, Gevers G, Raymaekers G, Devos P, Dequeker J (1990) Sex- and age-related changes in bone and serum osteocalcin. Calcif Tissue Int 46(3):179–182. Available from: Scholar
  245. Veeranki S, Tyagi SC (2015) Mechanisms of hyperhomocysteinemia induced skeletal muscle myopathy after ischemia in the CBS−/+ mouse model. Int J Mol Sci 16(1):1252–1265. Available from: Scholar
  246. Veeranki S, Givvimani S, Pushpakumar S, Tyagi SC (2014) Hyperhomocysteinemia attenuates angiogenesis through reduction of HIF-1 and PGC-1 levels in muscle fibers during hindlimb ischemia. AJP Hear Circ Physiol 306(8):H1116–H1127. Available from: Scholar
  247. Verlaan S, Aspray TJ, Bauer JM, Cederholm T, Hemsworth J, Hill TR et al (2017) Nutritional status, body composition, and quality of life in community-dwelling sarcopenic and non-sarcopenic older adults: a case-control study. Clin Nutr 36(1):267–274. Available from: Scholar
  248. Visser M, Kritchevsky SB, Newman AB, Goodpaster BH, Tylavsky FA, Nevitt MC, Harris TB (2005) Lower serum albumin concentration and change in muscle mass: the Health, Aging and Body Composition Study. Am J Clin Nutr 82(3):531–537. Available from: Scholar
  249. Walsh MC, Choi Y (2014) Biology of the RANKL-RANK-OPG system in immunity, bone, and beyond. Front Immunol 5(OCT):511. Available from: Scholar
  250. Wang J, Pei F, Tu C, Zhang H, Qiu X (2007) Serum bone turnover markers in patients with primary bone tumors. Oncology 72(5–6):338–342. Available from: Scholar
  251. Wee AKH (2016) Serum folate predicts muscle strength: a pilot cross-sectional study of the association between serum vitamin levels and muscle strength and gait measures in patients >65 years old with diabetes mellitus in a primary care setting. Nutr J 15(1):89. Available from: Scholar
  252. Weinstein RS (2011) Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med 365(1):62–70. Available from: Scholar
  253. Wikvall K (2001) Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form (review). Int J Mol Med 7(2):201–209. Available from: Scholar
  254. Wintermeyer E, Ihle C, Ehnert S, Stöckle U, Ochs G, de Zwart P et al (2016) Crucial role of vitamin D in the musculoskeletal system. Nutrients 8(6):319. Available from: Scholar
  255. Winzenberg T, van der Mei I, Mason RS, Nowson C, Jones G (2012) Vitamin D and the musculoskeletal health of older adults. Aust Fam Physician 41(3):92–99. Available from: Scholar
  256. Woitge HW, Pecherstorfer M, Li Y, Keck AV, Horn E, Ziegler R et al (1999) Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices. J Bone Miner Res 14(5):792–801. Available from: Scholar
  257. Yau MS, Yerges-Armstrong LM, Liu Y, Lewis CE, Duggan DJ, Renner JB et al (2017) Genome-Wide Association Study of radiographic knee osteoarthritis in North American caucasians. Arthritis Rheumatol 69(2):343–351PubMedPubMedCentralCrossRefGoogle Scholar
  258. Yazdanpanah N, Zillikens MC, Rivadeneira F, de Jong R, Lindemans J, Uitterlinden AG et al (2007) Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam Study. Bone 41(6):987–994. Available from: Scholar
  259. Zanker J, Duque G (2018) Osteoporosis in older persons: old and new players. J Am Geriatr Soc. Available from:
  260. Zeng L, Akasaki Y, Sato K, Ouchi N, Izumiya Y, Walsh K (2010) Insulin-like 6 is induced by muscle injury and functions as a regenerative factor. J Biol Chem 285(46):36060–36069PubMedPubMedCentralCrossRefGoogle Scholar
  261. Zhou J, Liu T, Wang W (2018) Prognostic significance of matrix metalloproteinase 9 expression in osteosarcoma. Medicine (Baltimore) 97(44):e13051CrossRefGoogle Scholar
  262. Zoch ML, Clemens TL, Riddle RC (2016) New insights into the biology of osteocalcin. Bone 82:42–49. Available from: Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
  2. 2.Clinical Institute of Medical and Chemical Laboratory DiagnosticsMedical University of GrazGrazAustria

Personalised recommendations