Abstract
The fields of neuroscience and bone biology have recently converged following the discovery that bone remodeling is directly regulated by the brain. This work has defined bone remodeling as one of the cardinal physiological functions of the body, subject to homeostatic regulation and integrated with the other major physiological functions by the hypothalamus. Central to this discovery was the definition of the adipocyte-derived hormone leptin as a regulator of both arms of bone remodeling, formation and resorption, through its action on the ventromedial hypothalamus and subsequently via the sympathetic nervous system to osteoblasts. The characterization of the sympathetic nervous system as a regulator of bone remodeling has led to several large clinical studies demonstrating a substantial protective effect of ß-blockers, particularly ß1-blockers, on fracture risk. Studies in model organisms have reinforced the role of the central nervous system in the regulation of bone remodeling in vivo by the identification of several additional genes, namely cocaine and amphetamine regulated transcript (Cart), melanocortin 4 receptor (Mc4R), neuropeptide Y (NPY), Y2 receptor, cannabinoid receptor CB1 (Cnbr1), and the genes of the circadian clock. These genes have several common features, including high levels of expression in the hypothalamus and the ability to regulate other major physiological functions in addition to bone remodeling including energy homeostasis, body weight, and reproduction. We review the major pathways that define the new field of neuroskeletal biology and identify further avenues of inquiry.
Similar content being viewed by others
References
Bonewald LF (2002) Osteocytes: a proposed multifunctional bone cell. J Musculoskelet Neuronal Interact 2:239–241
Rodan GA, Martin TJ (2000) Therapeutic approaches to bone diseases. Science 289:1508–1514
Cooper C, Melton LJI (1996) Magnitude and impact of osteoporosis and fractures. In: Marcus R, Feldman D, Kelsey J (eds), Osteoporosis. Academic Press, San Diego, pp 419–434
Perkins R, Skirving AP (1987) Callus formation and the rate of healing of femoral fractures in patients with head injuries. J Bone Joint Surg Br 69:521–524
Freehafer AA, Mast WA (1965) Lower extremity fractures in patients with spinal-cord injury. J Bone Joint Surg Am 47:683–694
Aro H (1985) Effect of nerve injury on fracture healing. Callus formation studied in the rat. Acta Orthop Scand 56:233–237
Ramnemark A, Nyberg L, Lorentzon R, Englund U, Gustafson Y (1999) Progressive hemiosteoporosis on the paretic side and increased bone mineral density in the nonparetic arm the first year after severe stroke. Osteoporos Int 9:269–275
Dauty M, Perrouin Verbe B, Maugars Y, Dubois C, Mathe JF (2000) Supralesional and sublesional bone mineral density in spinal cord-injured patients. Bone 27:305–309
Poole KE, Reeve J, Warburton EA (2002) Falls, fractures, and osteoporosis after stroke: time to think about protection? Stroke 33:1432–1436
Pearson J, Dancis J, Axelrod F, Grover N (1975) The sural nerve in familial dysautonomia. J Neuropathol Exp Neurol 34:413–424
Hukkanen M, Konttinen YT, Santavirta S, Paavolainen P, Gu XH, Terenghi G, Polak JM (1993) Rapid proliferation of calcitonin gene-related peptide-immunoreactive nerves during healing of rat tibial fracture suggests neural involvement in bone growth and remodelling. Neuroscience 54:969–979
Li J, Ahmad T, Spetea M, Ahmed M, Kreicbergs A (2001) Bone reinnervation after fracture: a study in the rat. J Bone Miner Res 16:1505–1510
Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil T, Shen J, Vinson C, Rueger JM, Karsenty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207
Zigman JM, Elmquist JK (2003) From anorexia to obesity–the yin and yang of body weight control. Endocrinology 144:3749–3756
Ahima RS, Saper CB, Flier JS, Elmquist JK (2000) Leptin regulation of neuroendocrine systems. Front Neuroendocrinol 21:263–307
Guidobono F, Pagani F, Sibilia V, Netti C, Lattuada N, Rapetti D, Mrak E, Villa I, Cavani F, Bertoni L, Palumbo C, Ferretti M, Marotti G, Rubinacci A (2006) Different skeletal regional response to continuous brain infusion of leptin in the rat. Peptides 27:1426–1433
Pogoda P, Egermann M, Schnell JC, Priemel M, Schilling AF, Alini M, Schinke T, Rueger JM, Schneider E, Clarke I, Amling M (2006) Leptin inhibits bone formation not only in rodents, but also in sheep. J Bone Miner Res 21:1591–1599
Elefteriou F, Takeda S, Ebihara K, Magre J, Patano N, Kim CA, Ogawa Y, Liu X, Ware SM, Craigen WJ, Robert JJ, Vinson C, Nakao K, Capeau J, Karsenty G (2004) Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci USA 101:3258–3263
Cock TA, Back J, Elefteriou F, Karsenty G, Kastner P, Chan S, Auwerx J (2004) Enhanced bone formation in lipodystrophic PPARγhyp/hyp mice relocates haematopoiesis to the spleen. EMBO Rep 5:1007–1012
Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317
Dhillon H, Zigman JM, Ye C, Lee CE, McGovern RA, Tang V, Kenny CD, Christiansen LM, White RD, Edelstein EA, Coppari R, Balthasar N, Cowley MA, Chua S Jr, Elmquist JK, Lowell BB (2006) Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49:191–203
Cornish J, Callon KE, Bava U, Lin C, Naot D, Hill BL, Grey AB, Broom N, Myers DE, Nicholson GC, Reid IR (2002) Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol 175:405–415
Burguera B, Hofbauer LC, Thomas T, Gori F, Evans GL, Khosla S, Riggs BL, Turner RT (2001) Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology 142:3546–3553
Steppan CM, Crawford DT, Chidsey-Frink KL, Ke H, Swick AG (2000) Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 92:73–78
Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL (1999) Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 140:1630–1638
Reseland JE, Syversen U, Bakke I, Qvigstad G, Eide LG, Hjertner O, Gordeladze JO, Drevon CA (2001) Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res 16:1426–1433
Di Monaco M, Vallero F, Di Monaco R, Mautino F, Cavanna A (2003) Fat body mass, leptin and femur bone mineral density in hip-fractured women. J Endocrinol Invest 26:1180–1185
Hamrick MW, Pennington C, Newton D, Xie D, Isales C (2004) Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone 34:376–383
Weiss LA, Barrett-Connor E, von Muhlen D, Clark P (2006) Leptin predicts BMD and bone resorption in older women but not older men: the Rancho Bernardo Study. J Bone Miner Res 21:758–764
Chanprasertyothin S, Piaseu N, Chailurkit L, Rajatanavin R, Ongphiphadhanakul B (2005) Association of circulating leptin with bone mineral density in males and females. J Med Assoc Thai 88:655–659
Blum M, Harris SS, Must A, Naumova EN, Phillips SM, Rand WM, Dawson-Hughes B (2003) Leptin, body composition and bone mineral density in premenopausal women. Calcif Tissue Int 73:27–32
Ruhl CE, Everhart JE (2002) Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res 17:1896–1903
Roux C, Arabi A, Porcher R, Garnero P (2003) Serum leptin as a determinant of bone resorption in healthy postmenopausal women. Bone 33:847–852
Thomas T, Burguera B, Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Riggs BL, Khosla S (2001) Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone 29:114–120
Sato M, Takeda N, Sarui H, Takami R, Takami K, Hayashi M, Sasaki A, Kawachi S, Yoshino K, Yasuda K (2001) Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab 86:5273–5276
Garnett SP, Hogler W, Blades B, Baur LA, Peat J, Lee J, Cowell CT (2004) Relation between hormones and body composition, including bone, in prepubertal children. Am J Clin Nutr 80:966–972
Roemmich JN, Clark PA, Mantzoros CS, Gurgol CM, Weltman A, Rogol AD (2003) Relationship of leptin to bone mineralization in children and adolescents. J Clin Endocrinol Metab 88:599–604
Oh KW, Lee WY, Rhee EJ, Baek KH, Yoon KH, Kang MI, Yun EJ, Park CY, Ihm SH, Choi MG, Yoo HJ, Park SW (2005) The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin Endocrinol (Oxf) 63:131–138
Papadopoulou F, Krassas GE, Kalothetou C, Koliakos G, Constantinidis TC (2004) Serum leptin values in relation to bone density and growth hormone-insulin like growth factors axis in healthy men. Arch Androl 50:97–103
Zhong N, Wu XP, Xu ZR, Wang AH, Luo XH, Cao XZ, Xie H, Shan PF, Liao EY (2005) Relationship of serum leptin with age, body weight, body mass index, and bone mineral density in healthy mainland Chinese women. Clin Chim Acta 351:161–168
Sahin G, Polat G, Baethis S, Milcan A, Baethdatoethlu O, Erdoethan C, Camdeviren H (2003) Body composition, bone mineral density, and circulating leptin levels in postmenopausal Turkish women. Rheumatol Int 23:87–91
Rauch F, Blum WF, Klein K, Allolio B, Schonau E (1998) Does leptin have an effect on bone in adult women? Calcif Tissue Int 63:453–455
Yamauchi M, Sugimoto T, Yamaguchi T, Nakaoka D, Kanzawa M, Yano S, Ozuru R, Sugishita T, Chihara K (2001) Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol (Oxf) 55:341–347
Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, Nicholson GC (2001) Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab 86:1884–1887
Gibson WT, Farooqi IS, Moreau M, DePaoli AM, Lawrence E, O’Rahilly S, Trussell RA (2004) Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab 89:4821–4826
Kishida Y, Hirao M, Tamai N, Nampei A, Fujimoto T, Nakase T, Shimizu N, Yoshikawa H, Myoui A (2005) Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification. Bone 37:607–621
Thorsell A, Heilig M (2002) Diverse functions of neuropeptide Y revealed using genetically modified animals. Neuropeptides 36:182–193
Bjurholm A, Kreicbergs A, Terenius L, Goldstein M, Schultzberg M (1988) Neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide-immunoreactive nerves in bone and surrounding tissues. J Auton Nerv Syst 25:119–125
Hill EL, Elde R (1991) Distribution of CGRP-, VIP-, D beta H-, SP-, and NPY-immunoreactive nerves in the periosteum of the rat. Cell Tissue Res 264:469–480
Baldock PA, Sainsbury A, Couzens M, Enriquez RF, Thomas GP, Gardiner EM, Herzog H (2002) Hypothalamic Y2 receptors regulate bone formation. J Clin Invest 109:915–921
Sainsbury A, Schwarzer C, Couzens M, Herzog H (2002) Y2 receptor deletion attenuates the type 2 diabetic syndrome of ob/ob mice. Diabetes 51:3420–3427
Wilding JP, Gilbey SG, Bailey CJ, Batt RA, Williams G, Ghatei MA, Bloom SR (1993) Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology 132:1939–1944
Baldock PA, Sainsbury A, Allison S, Lin EJ, Couzens M, Boey D, Enriquez R, During M, Herzog H, Gardiner EM (2005) Hypothalamic control of bone formation: distinct actions of leptin and Y2 receptor pathways. J Bone Miner Res 20:1851–1857
Baldock PA, Allison S, McDonald MM, Sainsbury A, Enriquez RF, Little DG, Eisman JA, Gardiner EM, Herzog H (2006) Hypothalamic regulation of cortical bone mass: opposing activity of Y2 receptor and leptin pathways. J Bone Miner Res 21:1600–1607
Sainsbury A, Baldock PA, Schwarzer C, Ueno N, Enriquez RF, Couzens M, Inui A, Herzog H, Gardiner EM (2003) Synergistic effects of Y2 and Y4 receptors on adiposity and bone mass revealed in double knockout mice. Mol Cell Biol 23:5225–5233
Baldock PA, Allison S, Sainsbury A, Enriquez RF, Gardiner EM, Herzog H, Eisman JA (2006) Hypothalamic neuropeptide Y exerts a negative effect on cortical bone formation. In: Abstracts of the 28th annual meeting of the American Society for Bone and Mineral Research September 2006. JBMR, vol 21 (suppl 1). Abstract no S65, p 1246
Elefteriou F, Takeda S, Liu X, Armstrong D, Karsenty G (2003) Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass. Endocrinology 144:3842–3847
Lutz B (2002) Molecular biology of cannabinoid receptors. Prostaglandins Leukot Essent Fatty Acids 66:123–142
Idris AI, van’t Hof RJ, Greig IR, Ridge SA, Baker D, Ross RA, Ralston SH (2005) Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat Med 11:774–779
Tam J, Ofek O, Fride E, Ledent C, Gabet Y, Muller R, Zimmer A, Mackie K, Mechoulam R, Shohami E, Bab I (2006) Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling. Mol Pharmacol 70:786–792
Ravinet Trillou C, Delgorge C, Menet C, Arnone M, Soubrie P (2004) CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 28:640–648
Ishac EJ, Jiang L, Lake KD, Varga K, Abood ME, Kunos G (1996) Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB1 receptors on peripheral sympathetic nerves. Br J Pharmacol 118:2023–2028
Ofek O, Karsak M, Leclerc N, Fogel M, Frenkel B, Wright K, Tam J, Attar-Namdar M, Kram V, Shohami E, Mechoulam R, Zimmer A, Bab I (2006) Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci USA 103:696–701
Tam J, Alexandrovich A, Di Marzo V, Petrosino S, Trembovler V, Zimmer A, Ledent C, Mackie K, Mechoulam R, Shohami E, Bab I (2006) CB1, but not CB2 cannabinoid receptor mediates stimulation of bone formation induced by traumatic brain injury. Abstracts of the 28th Annual Meeting of the American Society for Bone and Mineral Research September 2006. JBMR, vol 21 (suppl 1). Abstract no 1032, p S10
Devoto M, Shimoya K, Caminis J, Ott J, Tenenhouse A, Whyte MP, Sereda L, Hall S, Considine E, Williams CJ, Tromp G, Kuivaniemi H, Ala-Kokko L, Prockop DJ, Spotila LD (1998) First-stage autosomal genome screen in extended pedigrees suggests genes predisposing to low bone mineral density on chromosomes 1p, 2p and 4q. Eur J Hum Genet 6:151–157
Karsak M, Cohen-Solal M, Freudenberg J, Ostertag A, Morieux C, Kornak U, Essig J, Erxlebe E, Bab I, Kubisch C, de Vernejoul MC, Zimmer A (2005) Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum Mol Genet 14:3389–3396
Douglass J, McKinzie AA, Couceyro P (1995) PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine. J Neurosci 15:2471–2481
Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup S (1998) Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393:72–76
Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514–520
Ahn JD, Dubern B, Lubrano-Berthelier C, Clement K, Karsenty G (2006) Cart overexpression is the only identifiable cause of high bone mass in melanocortin 4 receptor deficiency. Endocrinology 147:3196–3202
Orwoll B, Bouxsein ML, Marks DL, Cone RD, Klein RF (2004) Increased bone mass and strength in melanocortin-4 receptor-deficient mice. In: Orthopaedic Research Society/American Academy of Orthopaedic Surgeons Presentations 2003, 71st Annual Meeting of the AAOS. San Francisco, CA
Aguirre J, Buttery L, O’Shaughnessy M, Afzal F, Fernandez de Marticorena I, Hukkanen M, Huang P, MacIntyre I, Polak J (2001) Endothelial nitric oxide synthase gene-deficient mice demonstrate marked retardation in postnatal bone formation, reduced bone volume, and defects in osteoblast maturation and activity. Am J Pathol 158:247–257
Armour KE, Armour KJ, Gallagher ME, Godecke A, Helfrich MH, Reid DM, Ralston SH (2001) Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase. Endocrinology 142:760–766
van’t Hof RJ, Ralston SH (1997) Cytokine-induced nitric oxide inhibits bone resorption by inducing apoptosis of osteoclast progenitors and suppressing osteoclast activity. J Bone Miner Res 12:1797–1804
van’t Hof RJ, Armour KJ, Smith LM, Armour KE, Wei XQ, Liew FY, Ralston SH (2000) Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption. Proc Natl Acad Sci USA 97:7993–7998
Lowik CW, Nibbering PH, van de Ruit M, Papapoulos SE (1994) Inducible production of nitric oxide in osteoblast-like cells and in fetal mouse bone explants is associated with suppression of osteoclastic bone resorption. J Clin Invest 93:1465–1472
van’t Hof RJ, Macphee J, Libouban H, Helfrich MH, Ralston SH (2004) Regulation of bone mass and bone turnover by neuronal nitric oxide synthase. Endocrinology 145:5068–5074
Perkins MN, Rothwell NJ, Stock MJ, Stone TW (1981) Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature 289:401–402
Satoh N, Ogawa Y, Katsuura G, Numata Y, Tsuji T, Hayase M, Ebihara K, Masuzaki H, Hosoda K, Yoshimasa Y, Nakao K (1999) Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion. Diabetes 48:1787–1793
Elefteriou F (2005) Neuronal signaling and the regulation of bone remodeling. Cell Mol Life Sci 62:2339–2349
Bonnet N, Benhamou CL, Brunet-Imbault B, Arlettaz A, Horcajada MN, Richard O, Vico L, Collomp K, Courteix D (2005) Severe bone alterations under beta2 agonist treatments: bone mass, microarchitecture and strength analyses in female rats. Bone 37:622–633
Minkowitz B, Boskey AL, Lane JM, Pearlman HS, Vigorita VJ (1991) Effects of propranolol on bone metabolism in the rat. J Orthop Res 9:869–875
Pierroz D, Baldock P, Bouxsein ML, Ferrari S (2006) Low cortical bone mass in mice lacking beta 1 and beta 2 adrenergic receptors is associated with low bone formation and circulating IGF-1. Abstracts of the 28th Annual Meeting of the American Society for Bone and Mineral Research September 2006. JBMR, vol 21 (suppl 1). Abstract no 1091, p S26
Wiens M, Etminan M, Gill SS, Takkouche B (2006) Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies. J Intern Med 260:350–362
Rejnmark L, Vestergaard P, Mosekilde L (2006) Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertens 24:581–589
Schlienger RG, Kraenzlin ME, Jick SS, Meier CR (2004) Use of beta-blockers and risk of fractures. JAMA 292:1326–1332
Levasseur R, Marcelli C, Sabatier JP, Dargent-Molina P, Breart G (2005) Beta-blocker use, bone mineral density, and fracture risk in older women: results from the Epidemiologie de l’Osteoporose prospective study. J Am Geriatr Soc 53:550–552
Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, Li L, Brancorsini S, Sassone-Corsi P, Townes TM, Hanauer A, Karsenty G (2004) ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell 117:387–398
Reid IR, Lucas J, Wattie D, Horne A, Bolland M, Gamble GD, Davidson JS, Grey AB (2005) Effects of a beta-blocker on bone turnover in normal postmenopausal women: a randomized controlled trial. J Clin Endocrinol Metab 90:5212–5216
Denes A, Boldogkoi Z, Uhereczky G, Hornyak A, Rusvai M, Palkovits M, Kovacs KJ (2005) Central autonomic control of the bone marrow: multisynaptic tract tracing by recombinant pseudorabies virus. Neuroscience 134:947–963
Mauer AM (1965) Diurnal variation of proliferative activity in the human bone marrow. Blood 26:1–7
Simmons DJ, Nichols G Jr (1966) Diurnal periodicity in the metabolic activity of bone tissue. Am J Physiol 210:411–418
Schlemmer A, Hassager C, Jensen SB, Christiansen C (1992) Marked diurnal variation in urinary excretion of pyridinium cross-links in premenopausal women. J Clin Endocrinol Metab 74:476–480
Srivastava AK, Bhattacharyya S, Li X, Mohan S, Baylink DJ (2001) Circadian and longitudinal variation of serum C-telopeptide, osteocalcin, and skeletal alkaline phosphatase in C3H/HeJ mice. Bone 29:361–367
Ladlow JF, Hoffmann WE, Breur GJ, Richardson DC, Allen MJ (2002) Biological variability in serum and urinary indices of bone formation and resorption in dogs. Calcif Tissue Int 70:186–193
Fu L, Patel MS, Bradley A, Wagner EF, Karsenty G (2005) The molecular clock mediates leptin-regulated bone formation. Cell 122:803–815
Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941
Rosen CJ, Morrison A, Zhou H, Storm D, Hunter SJ, Musgrave K, Chen T, Wei W, Holick MF (1994) Elderly women in northern New England exhibit seasonal changes in bone mineral density and calciotropic hormones. Bone Miner 25:83–92
Dawson-Hughes B, Dallal GE, Krall EA, Harris S, Sokoll LJ, Falconer G (1991) Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Intern Med 115:505–512
Ko CH, Takahashi JS (2006) Molecular components of the mammalian circadian clock. Hum Mol Genet 15(special issue 2):R271–R277
Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, Schibler U (2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14:2950–2961
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article is available at http://dx.doi.org/10.1007/s00223-007-9068-3.
Rights and permissions
About this article
Cite this article
Patel, M.S., Elefteriou, F. The New Field of Neuroskeletal Biology. Calcif Tissue Int 80, 337–347 (2007). https://doi.org/10.1007/s00223-007-9015-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00223-007-9015-3