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Osteoporosis: an evolutionary perspective

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Abstract

Increased life expectancy has led to an overall aging of the population and greater numbers of elderly people. Therefore, the number of people with osteoporosis has increased substantially, accompanied with an epidemic of hip fractures. Osteoporosis is an age-related systemic condition that naturally occurs, among mammals, only in humans. Osteoporosis is known to be highly heritable. However, assuming a genetic determinant for this post-reproductive disease to be transmitted from one generation to the next is counter-intuitive, based on the principles of human evolution, I will attempt to provide an explanation of the phenomenon from the point of view of evolution, selection, and changed environment in humans, which contributed to human longevity, while on other hand, contribute to diseases of civilization, including osteoporosis. There is a need to delve into evolution of human species in search for adaptive patterns to a specific environment that humans are operating in the last couple of millennia, to clarify whether “good” and “bad” genes exist, and how to find and correct them. The answer to the above questions will help us to identify causes of the current epidemic of osteoporosis and to pin-point a tailored treatment.

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References

  • Adams DJ, Spirt AA, Brown TD, Fritton SP, Rubin CT, Brand RA (1997) Testing the daily stress stimulus theory of bone adaptation with natural and experimentally controlled strain histories. J Biomech 30:671–678

    Article  PubMed  CAS  Google Scholar 

  • Alexander C (2001) Idiopathic osteoporosis: an evolutionary dys-adaptation? Ann Rheum Dis 60:554–558

    Article  PubMed  CAS  Google Scholar 

  • Bagge M (2000) A model of bone adaptation as an optimization process. J Biomech 33:1349–1357

    Article  PubMed  CAS  Google Scholar 

  • Baker ME (2001) Adrenal and sex steroid receptor evolution: environmental implications. J Mol Endocrinol 26:119–125

    Article  PubMed  CAS  Google Scholar 

  • Batchelder T (2005) The stories bones tell. The Townsend Letter Group

  • Beck TJ, Looker AC, Ruff CB, Sievanen H, Wahner HW (2000) Structural trends in the aging femoral neck and proximal shaft: analysis of the Third National Health and Nutrition Examination Survey dual-energy X-ray absorptiometry data. J Bone Miner Res 15:2297–2304

    Article  PubMed  CAS  Google Scholar 

  • Berry SD, Kiel DP (2007) Absolute risk for subsequent fracture was similar in women and men. ACP J Club 147:22

    PubMed  Google Scholar 

  • Bischoff HA, Borchers M, Gudat F, Duermueller U, Theiler R, Stahelin HB, Dick W (2001) In situ detection of 1, 25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J 33:19–24

    Article  PubMed  CAS  Google Scholar 

  • Bischoff-Ferrari HA, Borchers M, Gudat F, Durmuller U, Stahelin HB, Dick W (2004) Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 19:265–269

    Article  PubMed  CAS  Google Scholar 

  • Bonjour JP, Theintz G, Law F, Slosman D, Rizzoli R (1994) Peak bone mass. Osteoporos Int 4:7–13

    Article  PubMed  Google Scholar 

  • Booth FW, Lees SJ (2007) Fundamental questions about genes, inactivity, and chronic diseases. Physiol Genomics 28:146–157

    PubMed  CAS  Google Scholar 

  • Brandao-Burch A, Utting JC, Orriss IR, Arnett TR (2005) Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcif Tissue Int 77:167–174

    Article  PubMed  CAS  Google Scholar 

  • Burger H, de Laet CE, van Daele PL, Weel AE, Witteman JC, Hofman A, Pols HA (1998) Risk factors for increased bone loss in an elderly population: the Rotterdam Study. Am J Epidemiol 147:871–879

    PubMed  CAS  Google Scholar 

  • Capri M, Salvioli S, Monti D, Caruso C, Candore G, Vasto S, Olivieri F, Marchegiani F, Sansoni P, Baggio G, Mari D, Passarino G, De Benedictis G, Franceschi C (2008) Human longevity within an evolutionary perspective: the peculiar paradigm of a post-reproductive genetics. Exp Gerontol 43:53–60

    Article  PubMed  Google Scholar 

  • Conrad DF, Hurles ME (2007) The population genetics of structural variation. Nat Genet 39:S30–S36

    Article  PubMed  CAS  Google Scholar 

  • Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J (2005) Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 81:341–354

    PubMed  CAS  Google Scholar 

  • Fang Y, van Meurs JB, Rivadeneira F, van Schoor NM, van Leeuwen JP, Lips P, Pols HA, Uitterlinden AG (2007) Vitamin D receptor gene haplotype is associated with body height and bone size. J Clin Endocrinol Metab 92:1491–1501

    Article  PubMed  CAS  Google Scholar 

  • Ferrari S (2005) Osteoporosis: a complex disorder of aging with multiple genetic and environmental determinants. In: Simopoulos A (ed) Nutrition and fitness: mental health, aging, and the implementation of a healthy diet and physical activity lifestyle, vol 95. Karger, Basel, pp 35–51

    Chapter  Google Scholar 

  • Ferrari SL, Rizzoli R (2005) Gene variants for osteoporosis and their pleiotropic effects in aging. Mol Aspects Med 26:145–167

    Article  PubMed  CAS  Google Scholar 

  • Ferrari SL, Karasik D, Liu J, Karamohamed S, Herbert AG, Cupples LA, Kiel DP (2004) Interactions of interleukin-6 promoter polymorphisms with dietary and lifestyle factors and their association with bone mass in men and women from the Framingham Osteoporosis Study. J Bone Miner Res 19:552–559

    Article  PubMed  CAS  Google Scholar 

  • Ferretti JL, Capozza RF, Cointry GR, Garcia SL, Plotkin H, Alvarez Filgueira ML, Zanchetta JR (1998) Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. Bone 22:683–690

    Article  PubMed  CAS  Google Scholar 

  • Frost HM (1999) On the estrogen-bone relationship and postmenopausal bone loss: a new model. J Bone Miner Res 14:1473–1477

    Article  PubMed  CAS  Google Scholar 

  • Fuller K (2000) Lactose, rickets, and the coevolution of genes and culture. J Hum Ecol 28:471–477

    Article  Google Scholar 

  • Gennari L, Masi L, Merlotti D, Picariello L, Falchetti A, Tanini A, Mavilia C, Del Monte F, Gonnelli S, Lucani B, Gennari C, Brandi ML (2004) A polymorphic CYP19 TTTA repeat influences aromatase activity and estrogen levels in elderly men: effects on bone metabolism. J Clin Endocrinol Metab 89:2803–2810

    Article  PubMed  CAS  Google Scholar 

  • Grainger S, Beise J (2004) Menopause and post-generative longevity: testing the ‘stopping-early’ and ‘grandmother’ hypotheses. MPIDR Working Papers Vol http://www.demogr.mpg.de/papers/working/wp-2004-003.pdf

  • Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A (2004) Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 150:323–328

    Article  PubMed  CAS  Google Scholar 

  • Gurel I, Livshits G (2003) Phylogeny of vertebrate nuclear receptors—analysis of variance components in protein sequences. Coll Antropol 27:599–610

    PubMed  CAS  Google Scholar 

  • Hannan MT, Felson DT, Dawson-Hughes B, Tucker KL, Cupples LA, Wilson PW, Kiel DP (2000) Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res 15:710–720

    Article  PubMed  CAS  Google Scholar 

  • Harris EE, Malyango AA (2005) Evolutionary explanations in medical and health profession courses: are you answering your students’ “why” questions? BMC Med Educ 5:16

    Article  PubMed  Google Scholar 

  • Ho AM, Marker PC, Peng H, Quintero AJ, Kingsley DM, Huard J (2008) Dominant negative Bmp5 mutation reveals key role of BMPs in skeletal response to mechanical stimulation. BMC Dev Biol 8:35

    Article  PubMed  CAS  Google Scholar 

  • http://www.nof.org/osteoporosis/diseasefacts.htm (2008) National Osteoporosis Foundation

  • Karasik D, Ferrari SL (2008) Contribution of gender-specific genetic factors to osteoporosis risk. Ann Hum Genet 72:696–714

    Article  PubMed  CAS  Google Scholar 

  • Karasik D, Kiel DP (2008) Genetics of the musculoskeletal system: a pleiotropic approach. J Bone Miner Res 23:788–802

    Article  PubMed  CAS  Google Scholar 

  • Karasik D, Arensburg B, Tillier A-M, Pavlovsky O (1998) Skeletal age assessment of fossil hominids. J Archaeol Sci 25:689–696

    Article  Google Scholar 

  • Karasik D, Arensburg B, Pavlovsky OM (2000) Age assessment of Natufian remains from the land of Israel. Am J Phys Anthropol 113:263–274

    Article  PubMed  CAS  Google Scholar 

  • Khoury MJ, McCabe LL, McCabe ER (2003) Population screening in the age of genomic medicine. N Engl J Med 348:50–58

    Article  PubMed  CAS  Google Scholar 

  • Kiel DP, Demissie S, Dupuis J, Lunetta KL, Murabito JM, Karasik D (2007a) Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 8(Suppl 1):S14

    Article  PubMed  CAS  Google Scholar 

  • Kiel DP, Ferrari SL, Cupples LA, Karasik D, Manen D, Imamovic A, Herbert AG, Dupuis J (2007b) Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 40:587–596

    Article  PubMed  CAS  Google Scholar 

  • Kirkwood TB, Rose MR (1991) Evolution of senescence: late survival sacrificed for reproduction. Philos Trans R Soc Lond B Biol Sci 332:15–24

    Article  PubMed  CAS  Google Scholar 

  • Langdahl BL, Uitterlinden AG, Ralston SH (2008) Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study. Bone. Available online 3 December 2007

  • Latimer B (2005) The perils of being bipedal. Ann Biomed Eng 33:3–6

    Article  PubMed  Google Scholar 

  • Mayhew PM, Thomas CD, Clement JG, Loveridge N, Beck TJ, Bonfield W, Burgoyne CJ, Reeve J (2005) Relation between age, femoral neck cortical stability, and hip fracture risk. Lancet 366:129–135

    Article  PubMed  Google Scholar 

  • Mays S (2000) Age-dependent cortical bone loss in women from 18th and early 19th century London. Am J Phys Anthropol 112:349–361

    Article  PubMed  CAS  Google Scholar 

  • Mays S (2001) Effects of age and occupation on cortical bone in a group of 18th–19th century British men. Am J Phys Anthropol 116:34–44

    Article  PubMed  CAS  Google Scholar 

  • Melton LJ (1995) How many women have osteoporosis now? J Bone Miner Res 10:175–177

    PubMed  Google Scholar 

  • Michaelsson K, Olofsson H, Jensevik K, Larsson S, Mallmin H, Berglund L, Vessby B, Melhus H (2007) Leisure physical activity and the risk of fracture in men. PLoS Med 4:e199

    Article  PubMed  Google Scholar 

  • Nowlan NC, Prendergast PJ (2005) Evolution of mechanoregulation of bone growth will lead to non-optimal bone phenotypes. J Theor Biol 235:408–418

    Article  PubMed  Google Scholar 

  • Peccei JS (2001) A critique of the grandmother hypotheses: old and new. Am J Hum Biol 13:434–452

    Article  PubMed  CAS  Google Scholar 

  • Ralston SH, de Crombrugghe B (2006) Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev 20:2492–2506

    Article  PubMed  CAS  Google Scholar 

  • Ralston SH, Uitterlinden AG, Brandi ML, Balcells S, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Scollen S, Bustamante M, Husted LB, Carey AH, Diez-Perez A, Dunning AM, Falchetti A, Karczmarewicz E, Kruk M, van Leeuwen JP, van Meurs JB, Mangion J, McGuigan FE, Mellibovsky L, del Monte F, Pols HA, Reeve J, Reid DM, Renner W, Rivadeneira F, van Schoor NM, Sherlock RE, Ioannidis JP (2006) Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med 3:e90

    Article  PubMed  CAS  Google Scholar 

  • Rauch F, Rittweger J (2007) Recent literature review: new studies on bone material, fractures, walking and running. J Musculoskelet Neuronal Interact 7:368–371

    Google Scholar 

  • Rubin CT, Sommerfeldt DW, Judex S, Qin Y (2001) Inhibition of osteopenia by low magnitude, high-frequency mechanical stimuli. Drug Discov Today 6:848–858

    Article  PubMed  Google Scholar 

  • Sievänen H (2005) Hormonal influences on the muscle-bone feedback system: a perspective. J Musculoskelet Neuronal Interact 5:255–261

    PubMed  Google Scholar 

  • Sockol MD, Raichlen DA, Pontzer H (2007) Chimpanzee locomotor energetics and the origin of human bipedalism. Proc Natl Acad Sci U S A 104:12265–12269

    Article  PubMed  CAS  Google Scholar 

  • Turner CH (2002) Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporosis Int 13:97–104

    Article  CAS  Google Scholar 

  • Turner CH, Takano Y, Owan I (1995) Aging changes mechanical loading thresholds for bone formation in rats. J Bone Miner Res 10:1544–1549

    Article  PubMed  CAS  Google Scholar 

  • Uitterlinden AG, Ralston SH, Brandi ML, Carey AH, Grinberg D, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Reeve J, Reid DM, Amedei A, Bassiti A, Bustamante M, Husted LB, Diez-Perez A, Dobnig H, Dunning AM, Enjuanes A, Fahrleitner-Pammer A, Fang Y, Karczmarewicz E, Kruk M, van Leeuwen JP, Mavilia C, van Meurs JB, Mangion J, McGuigan FE, Pols HA, Renner W, Rivadeneira F, van Schoor NM, Scollen S, Sherlock RE, Ioannidis JP (2006) The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann Intern Med 145:255–264

    PubMed  CAS  Google Scholar 

  • van Meurs JB, Trikalinos T, Ralston SH, GENOMOS C (2008) Large-scale analysis of association between polymorphisms in the LRP-5 and -6 genes and osteoporosis: the GENOMOS study. JAMA

  • Varki A, Altheide TK (2005) Comparing the human and chimpanzee genomes: searching for needles in a haystack. Genome Res 15:1746–1758

    Article  PubMed  CAS  Google Scholar 

  • Vieth R (2003) Vitamin D deficiency affecting genetic selection for lighter skin color. In: Agarwal SC, Stout SD (eds) Bone loss and osteoporosis: an anthropological perspective. Kluwer Academic Publications, New York

    Google Scholar 

  • Windelinckx A, De Mars G, Beunen G, Aerssens J, Delecluse C, Lefevre J, Thomis MA (2007) Polymorphisms in the vitamin D receptor gene are associated with muscle strength in men and women. Osteoporos Int 18:1235–1242

    Article  PubMed  CAS  Google Scholar 

  • Wolf JB, Pomp D, Eisen EJ, Cheverud JM, Leamy LJ (2006) The contribution of epistatic pleiotropy to the genetic architecture of covariation among polygenic traits in mice. Evol Dev 8:468–476

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are thankful to Genevieve Ferrick of Harvard Extension School and Catherine Gauthier of Hebrew SeniorLife for their critical reading, as well as to two anonymous reviewers for their useful comments. This review was supported, in part, by National Institute of Health/NIAMS grant (R01 AR050066).

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Correspondence to David Karasik.

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Karasik, D. Osteoporosis: an evolutionary perspective. Hum Genet 124, 349–356 (2008). https://doi.org/10.1007/s00439-008-0559-8

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