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Skeletal effects of long-term caloric restriction in rhesus monkeys

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Abstract

Age-related bone loss is well established in humans and is known to occur in nonhuman primates. There is little information, however, on the effect of dietary interventions, such as caloric restriction (CR), on age-related bone loss. This study examined the effects of long-term, moderate CR on skeletal parameters in rhesus monkeys. Thirty adult male rhesus monkeys were subjected to either a restricted (R, n = 15) or control (C, n = 15) diet for 20 years and examined throughout for body composition and biochemical markers of bone turnover. Total body, spine, and radius bone mass and density were assessed by dual-energy X-ray absorptiometry. Assessment of biochemical markers of bone turnover included circulating serum levels of osteocalcin, carboxyterminal telopeptide of type I collagen, cross-linked aminoterminal telopeptide of type I collagen, parathyroid hormone, and 25(OH)vitamin D. Overall, we found that bone mass and density declined over time with generally higher levels in C compared to R animals. Circulating serum markers of bone turnover were not different between C and R with nonsignficant diet-by-time interactions. We believe the lower bone mass in R animals reflects the smaller body size and not pathological osteopenia.

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References

  • Amin S (2010) Mechanical factors and bone health: effects of weightlessness and neurologic injury. Curr Rheumatol Rep 12(3):170–176. doi:10.1007/s11926-010-0096-z

    Article  PubMed  Google Scholar 

  • Barrett-Connor E, Siris ES, Wehren LE, Miller PD, Abbott TA, Berger ML, Santora AC, Sherwood LM (2005) Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res 20(2):185–194. doi:10.1359/JBMR.041007

    Article  PubMed  Google Scholar 

  • Berrigan D, Lavigne JA, Perkins SN, Nagy TR, Barrett JC, Hursting SD (2005) Phenotypic effects of calorie restriction and insulin-like growth factor-1 treatment on body composition and bone mineral density of C57BL/6 mice: implications for cancer prevention. In Vivo 19(4):667–674

    PubMed  CAS  Google Scholar 

  • Binkley N, Kimmel D, Bruner J, Haffa A, Davidowitz B, Meng C, Schaffer V, Green J (1998) Zoledronate prevents the development of absolute osteopenia following ovariectomy in adult rhesus monkeys. J Bone Miner Res 13(11):1775–1782. doi:10.1359/jbmr.1998.13.11.1775

    Article  PubMed  CAS  Google Scholar 

  • Black A, Allison DB, Shapses SA, Tilmont EM, Handy AM, Ingram DK, Roth GS, Lane MA (2001) Calorie restriction and skeletal mass in rhesus monkeys (Macaca mulatta): evidence for an effect mediated through changes in body size. J Gerontol Biol Sci 56A:B98–B107

    Article  CAS  Google Scholar 

  • Blain H, Vuillemin A, Teissier A, Hanesse B, Guillemin F, Jeandel C (2001) Influence of muscle strength and body weight and composition on regional bone mineral density in healthy women aged 60 years and over. Gerontology 47:207–212

    Article  PubMed  CAS  Google Scholar 

  • Bowden DM, Teets C, Witkin J, Young DM (1979) Long bone calcification and morphology. In: Bowden DM (ed) Aging in nonhuman primates, chapter 27. Van Nostrand Reinhold, New York, pp 335–355

    Google Scholar 

  • Brommage R (2001) Perspectives on using nonhuman primates to understand the etiology and treatment of postmenopausal osteoporosis. J Musculoskelet Neuronal Interact 1(4):307–325

    PubMed  CAS  Google Scholar 

  • Calbet JA, Moysi JS, Dorado C, Rodriguez LP (1998) Bone mineral content and density in professional tennis players. Calcif Tissue Int 62:491–496

    Article  PubMed  CAS  Google Scholar 

  • Carro E, Senaris R, Considine RV, Casanueva FF, Dieguez C (1997) Regulation of in vivo growth hormone secretion by leptin. Endocrinol 138(5):2203–2206

    Article  CAS  Google Scholar 

  • Cauley JA (2011) Defining ethnic and racial differences in osteoporosis and fragility fractures. Clin Orthop Relat Res 469:1891–1899. doi:10.1007/s11999-011-1863-5

    Article  PubMed  Google Scholar 

  • Champ JE, Binkley N, Havighurst T, Colman RJ, Kemnitz JW, Roecker EB (1996) The effect of advancing age on bone mineral content of the female rhesus monkey. Bone 19(5):485–492

    Article  PubMed  CAS  Google Scholar 

  • Colman RJ, Roecker EB, Ramsey JJ, Kemnitz JW (1998) The effect of dietary restriction on body composition in adult male and female rhesus macaques. Aging Clin Exp Res 10(2):83–92

    CAS  Google Scholar 

  • Colman RJ, Binkley N, Lane MA, Abbott DH, Kemnitz JW (1999a) Skeletal effects of aging and menopausal status in female rhesus macaques. J Clin Endocrinol Metab 84(11):4144–4148

    Article  PubMed  CAS  Google Scholar 

  • Colman RJ, Lane MA, Binkley N, Wegner FH, Kemnitz JW (1999b) Skeletal effects of aging in male rhesus monkeys. Bone 24(1):17–23

    Article  PubMed  CAS  Google Scholar 

  • Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325(5937):201–204. doi:10.1126/science.1173635

    Article  PubMed  CAS  Google Scholar 

  • DeRousseau CJ (1985) Aging in the musculoskeletal system of rhesus monkeys: III. Bone loss. Am J Phys Anthropol 68:157–167

    Article  PubMed  CAS  Google Scholar 

  • DiGiovanna AG (1994) Skeletal system. Human aging: biological perspectives. McGraw-Hill, New York, pp 165–183

  • Duncan AE, Colman RJ, Kramer PA (2011) Longitudinal study of radiographic spinal osteoarthritis in a macaque model. J Orthop Res 29:1152–1160. doi:10.1002/jor.21390

    Article  PubMed  Google Scholar 

  • Edelstein SL, Barrett-Connor E (1993) Relation between body size and bone mineral density in elderly men and women. Am J Epidemiol 138(3):160–169

    PubMed  CAS  Google Scholar 

  • Eisman JA, Sambrook PN, Kelly PJ, Pocock NA (1991) Exercise and its interaction with genetic influences in the determination of bone mineral density. Am J Med 91:5S–9S

    Article  PubMed  CAS  Google Scholar 

  • Fox J, Miller MA, Newman MK, Turner CH, Recker RR, Smith SY (2007) Treatment of skeletally mature ovariectomized rhesus monkeys with PTH(1-84) for 16 months increases bone formation and density and improves trabecular architecture and biomechanical properties at the lumbar spine. J Bone Miner Res 22(2):260–273. doi:10.1359/jbmr.061101

    Article  PubMed  CAS  Google Scholar 

  • Frost H (1993) Suggested fundamental concepts in skeletal physiology. Calcif Tissue Int 52:1–4

    Article  PubMed  CAS  Google Scholar 

  • Garn SM (1975) Bone-loss and aging. In: Goldman R, Rockstein M (eds) The physiology and pathology of human aging. Academic, New York, pp 39–57

    Google Scholar 

  • Grynpas MD, Huckell B, Protzker KPH, Hancock RGV, Kessler MJ (1989) Bone mineral and osteoporosis in aging rhesus monkeys. PR Health Sci J 8(1):197–204

    CAS  Google Scholar 

  • Grynpas MD, Huckell CB, Reichs KJ, DeRousseau CJ, Greenwood C, Kessler MJ (1993) Effect of age and osteoarthritis on bone mineral in rhesus monkey vertebrae. J Bone Miner Res 8(8):909–917

    Article  PubMed  CAS  Google Scholar 

  • Haapasalo H, Kannus P, Sievanen H, Pasanen M, Uusi-Rasi K, Heinonen A, Oja P, Vuori I (1998) Effect of long-term unilateral activity on bone mineral density of female junior tennis players. J Bone Miner Res 13:310–319

    Article  PubMed  CAS  Google Scholar 

  • Habold C, Momken I, Ouadi A, Bekaert V, Brasse D (2011) Effect of prior treatment with resveratrol on density and structure of rat long bones under tail-suspension. J Bone Miner Metab 29(1):15–22. doi:10.1007/s00774-010-0187-y

    Article  PubMed  CAS  Google Scholar 

  • Haffner SM, Bauer RL (1992) Excess androgenicity only partially explains the relationship between obesity and bone density in premenopausal women. Int J Obes 16:869–874

    CAS  Google Scholar 

  • Holloway WR, Collier FM, Aitken CJ, Myers DE, Hodge JM, Malakellis M, Gough TJ, Collier GR, Nicholson GC (2002) Leptin inhibits osteoclast generation. J Bone Miner Res 17(2):200–209. doi:10.1359/jbmr.2002.17.2.200

    Article  PubMed  CAS  Google Scholar 

  • Horowitz MC (1993) Cytokines and estrogen in bone: anti-osteoporotic effects. Science 260:626–627

    Article  PubMed  CAS  Google Scholar 

  • Hyldstrup L, Andersen T, McNair P, Breum L, Transbol I (1993) Bone metabolism in obesity: changes related to severe overweight and dietary weight reduction. Acta Endocrinol 129:393–398

    PubMed  CAS  Google Scholar 

  • Ingram DK, Cutler RG, Wendruch R, Renquist DM, Knapka JJ, April M, Belcher CT, Clark MA, Hatcherson CD, Marriott BM, Roth GS (1990) Dietary restriction and aging: the initiation of a primate study. J Gerontol Biol Sci 45(5):B148–B163

    CAS  Google Scholar 

  • Kalu DN, Hardin RH, Cockerham R, Yu BP (1984a) Aging and dietary modulation of rat skeleton and parathyroid hormone. Endocrinol 115(4):1239–1247

    Article  CAS  Google Scholar 

  • Kalu DN, Hardin RR, Cockerham R, Yu BP, Norling BK, Egan JW (1984b) Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats. Mech Age Dev 26:103–112

    Article  CAS  Google Scholar 

  • Kalu DN, Masoro EJ, Yu BP, Hardin RR, Hollis BW (1988) Modulation of age-related hyperparathyroidism and senile bone loss in fischer rats by soy protein and food restriction. Endocrinol 122(5):1847–1854

    Article  CAS  Google Scholar 

  • Karsenty G, Oury F (2010) The central regulation of bone mass, the first link between bone remodeling and energy metabolism. J Clin Endocrinol Metab 95(11):4795–4801. doi:10.1210/jc.2010-1030

    Article  PubMed  CAS  Google Scholar 

  • Kemnitz JW, Weindruch R, Roecker EB, Crawford K, Kaufman PL, Ershler WB (1993) Dietary restriction of adult male rhesus monkeys: design, methodology, and preliminary findings from the first year of study. J Gerontol Biol Sci 48(1):B17–B26

    CAS  Google Scholar 

  • Kessler MJ, Turnquist JE, Pritzker KPH (1986) Reduction of passive extension and radiographic evidence of degenerative knee joint diseases in cage-raised and free-ranging aged rhesus monkeys (Macaca mulatta). J Med Primatol 15:1–9

    PubMed  CAS  Google Scholar 

  • Lane MA, Reznick AZ, Tilmont EM, Lanir A, Ball SS, Read V, Ingram DK, Cutler RG, Roth GS (1995) Aging and food restriction alter some indices of bone metabolism in male rhesus monkeys (Macaca mulatta). J Nutr 125:1600–1610

    PubMed  CAS  Google Scholar 

  • Lane MA, Black A, Handy AM, Shapses SA, Tilmont EM, Kiefer TL, Ingram DK, Roth GS (2001) Energy restriction does not alter bone mineral metabolism or reproductive cycling and hormones in female rhesus monkeys. J Nutr 131:820–827

    PubMed  CAS  Google Scholar 

  • Lanyon LE, Rubin CT, Baust G (1986) Modulation of bone loss during calcium insufficiency by controlled dynamic loading. Calcif Tissue Int 38:209–216

    Article  PubMed  CAS  Google Scholar 

  • Maimoun L, Coste O, Mariano-Goulart D, Galtier F, Mura T, Philibert P, Briot K, Paris F, Sultan C (2011) In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels. Osteoporos Int 22:3055–3066. doi:10.1007/s00198-011-1541-1

    Article  PubMed  CAS  Google Scholar 

  • Markou KB, Theodoropoulou A, Tsekouras A, Vagenakis AG, Georgopoulos NA (2010) Bone acquisition during adolescence in athletes. Ann N Y Acad Sci 1205:12–16. doi:10.1111/j.1749-6632.2010.05675.x

    Article  PubMed  Google Scholar 

  • Masoro EJ, Austad SN (1996) The evolution of the antiaging action of dietary restriction: a hypothesis. J Gerontol Biol Sci 51A:B387–B397

    Article  CAS  Google Scholar 

  • Mattison JA, Lane MA, Roth GS, Ingram DK (2003) Calorie restriction in rhesus monkeys. Exp Gerontol 38(1–2):35–46

    Article  PubMed  Google Scholar 

  • Mazess RB (1982) On aging bone loss. Clin Orthop 165:239–252

    PubMed  Google Scholar 

  • McCay CM, Crowell MF, Maynard LA (1935) The effect of retarded growth upon the length of the lifespan and upon ultimate body size. J Nutr 10:63–79

    CAS  Google Scholar 

  • Miller LC, Weaver DS, McAlister JA, Koritnik DR (1986) Effects of ovariectomy on vertebral trabecular bone in the cynomolgus monkey (Macaca fascicularis). Calcif Tissue Int 38(1):62–65

    Article  PubMed  CAS  Google Scholar 

  • Mullender M, El Haj AJ, Yang Y, van Duin MA, Burger EH, Klein-Nulend J (2004) Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue. Med Biol Eng Comput 42(1):14–21

    Article  PubMed  CAS  Google Scholar 

  • Nuti R, Martini G, Gennari C (1995) Age-related changes of whole skeleton and body composition in healthy men. Calcif Tissue Int 57:336–339

    Article  PubMed  CAS  Google Scholar 

  • Pope NS, Gould KG, Anderson DC, Mann DR (1989) Effects of age and sex on bone density in the rhesus monkey. Bone 10:109–112

    Article  PubMed  CAS  Google Scholar 

  • Przybeck TR (1985) Histomorphology of the rib: bone mass and cortical remodeling. In: Davis RT, Leatleus CW (eds) Behavior and pathology of aging in rhesus monkeys. Alan R. Liss, New York, pp 303–326

    Google Scholar 

  • Qin W, Bauman WA, Cardozo C (2010) Bone and muscle loss after spinal cord injury: organ interactions. Ann N Y Acad Sci 1211:66–84. doi:10.1111/j.1749-6632.2010.05806.x

    Article  PubMed  Google Scholar 

  • Ramsdale SJ, Bassey EJ (1994) Changes in bone mineral density associated with dietary-induced loss of body mass in young women. Clin Sci 87:343–348

    PubMed  CAS  Google Scholar 

  • Ramsey JJ, Colman RJ, Binkley NC, Christensen JD, Gresl TA, Kemnitz JW, Weindruch R (2000) Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study. Exp Gerontol 35(9–10):1131–1149

    Article  PubMed  CAS  Google Scholar 

  • Redman LM, Rood J, Anton SD, Champagne C, Smith SR, Ravussin E (2008) Calorie restriction and bone health in young, overweight individuals. Arch Intern Med 168(17):1859–1866. doi:10.1001/archinte.168.17.1859

    Article  PubMed  Google Scholar 

  • Sanderson JP, Binkley N, Roecker EB, Champ JE, Pugh TD, Aspnes L, Weindruch R (1997) Influence of fat intake and caloric restriction on bone in aging male rats. J Gerontol Biol Sci 52A(1):B20–B25

    Article  Google Scholar 

  • Smith SY, Jolette J, Turner CH (2009) Skeletal health: primate model of postmenopausal osteoporosis. Am J Primatol 71(9):752–765. doi:10.1002/ajp.20715

    Article  PubMed  CAS  Google Scholar 

  • Syed FA, Hoey KA (2010) Integrative physiology of the aging bone: insights from animal and cellular models. Ann N Y Acad Sci 1211:95–106. doi:10.1111/j.1749-6632.2010.05813.x

    Article  PubMed  Google Scholar 

  • Talbott SM, Rothkopf MM, Shapses SA (1998) Dietary restriction of energy and calcium alters bone turnover and density in younger and older female rats. J Nutr 128:640–645

    PubMed  CAS  Google Scholar 

  • 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. Endocrinol 140(4):1630–1638

    Article  CAS  Google Scholar 

  • Turner CH, Pavalko FM (1998) Mechanotransduction and functional response of the skeleton to physical stress: the mechanisms and mechanics of bone adaptation. J Orthop Sci 3(6):346–355

    Article  PubMed  CAS  Google Scholar 

  • Vernikos J, Schneider VS (2010) Space, gravity and the physiology of aging: parallel or convergent disciplines? A mini-review. Gerontology 56(2):157–166. doi:10.1159/000252852

    Article  PubMed  Google Scholar 

  • Villareal DT, Kotyk JJ, Armamento-Villareal RC, Kenguva V, Seaman P, Shahar A, Wald MJ, Kleerekoper M, Fontana L (2011) Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition. Aging Cell 10(1):96–102. doi:10.1111/j.1474-9726.2010.00643.x

    Article  PubMed  CAS  Google Scholar 

  • Wardlaw GM (1996) Putting body weight and osteoporosis into perspective. Am J Clin Nutr 63(Supplement):433S–436S

    PubMed  CAS  Google Scholar 

  • Weindruch R (1996) Caloric restriction and aging. Sci Am 274:46–52

    Google Scholar 

  • Weindruch R, Walford RL (1988) The retardation of aging and disease by dietary restriction. Charles C. Thomas, Springfield

    Google Scholar 

  • Westerbeek ZW, Hepple RT, Zernicke RF (2008) Effects of aging and caloric restriction on bone structure and mechanical properties. J Gerontol A Biol Sci Med Sci 63(11):1131–1136

    Article  PubMed  Google Scholar 

  • Wheadon GD, Heaney RP (1993) Effects of physical inactivity, paralysis, and weightlessness on bone growth. In: Hall BK (ed) Bone growth, vol 7. CRC, Boca Raton

    Google Scholar 

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Acknowledgements

We acknowledge the excellent technical assistance provided by S. Baum, J. Christensen, J. A. Adriansjach, C. E. Armstrong, and the Animal Care and Veterinary Staff of the WNPRC. This work was supported by National Institutes of Health grants P01 AG-11915 and P51 RR000167. This research was conducted in part at the WNPRC, which received support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. This research was supported in part by facilities and resources at the Wm. S. Middleton Memorial Veterans Hospital.

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Authors and Affiliations

  1. Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, 53715, USA

    Ricki J. Colman

  2. Department of Biostatistics, University of Alabama, Birmingham, AL, 35294, USA

    T. Mark Beasley & David B. Allison

  3. Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53706, USA

    Richard Weindruch

  4. Geriatric Research, Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, 53705, USA

    Richard Weindruch

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  1. Ricki J. Colman
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  2. T. Mark Beasley
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  4. Richard Weindruch
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Correspondence to Ricki J. Colman.

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Colman, R.J., Beasley, T.M., Allison, D.B. et al. Skeletal effects of long-term caloric restriction in rhesus monkeys. AGE 34, 1133–1143 (2012). https://doi.org/10.1007/s11357-011-9354-x

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