Skip to main content
SpringerLink
Log in

Molekulare Mechanismen altersspezifischer Veränderungen des Kalzium- und Knochenstoffwechsels

  • Chapter
Molekularmedizinische Grundlagen von altersspezifischen Erkrankungen

Part of the book series: Molekulare Medizin ((MOLMED))

Zusammenfassung

Die Alterung von Zellen ist ein generelles Lebensphänomen. Sie betrifft die beiden grundlegenden Fähigkeiten der Zellen, die Fähigkeit zur Vermehrung sowie die Entwicklung und Ausführung zellspezifischer Leistungen nach ihrer Differenzierung. Die Erforschung der Ursachen zellulärer Alterungsvorgänge führt in zwei unterschiedliche Richtungen. Eine Forschungsrichtung begreift Altern als ein genetisches Programm, welches unter anderem beinhaltet, dass die Proliferationskapazität der Zellen geringer wird. Dies hat zur Folge, dass die Regeneration von Geweben durch den regelmäßigen Ersatz differenzierter Zellen im Alter abnimmt, aber auch das Risiko der Entstehung von Tumoren reduziert wird. Die andere Forschungsrichtung führt altersassoziierte Phänomene veränderter zellulärer Funktion vorwiegend darauf zurück, dass oxidative Vorgänge zelluläre Proteine verändern und in ihrer Funktion beeinträchtigen. Solche Phänomene werden auch bei Proteinen beobachtet, die mit dem Knochenstoffwechsel, der Kalziumhomöostase und dem intrazellulären Signalling durch Kalzium verknüpft sind. Die beiden verschiedenen Mechanismen der Zellalterung, auch als replikative und postreplikative Mechanismen bezeichnet, interagieren miteinander und sind im Grunde nicht vollständig voneinander zu trennen (Übersichten bei Campisi 2001, Kuro-o 2001).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  • Agnusdei D, Civitelli R, Camporeale A, Parisi G, Gennari L, Nardi P, Gennari C (1998) Age-related decline of bone mass and intestinal calcium absorption in normal males. Calcif Tissue Int 63:197–201

    PubMed  CAS  Google Scholar 

  • Alevizaki CC, Ikkos DG, Singhelakis P (1973) Progressive decrease of true intestinal calcium absorption with age in normal man. J Nucl Med 14:760–762

    PubMed  CAS  Google Scholar 

  • Ammann P, Rizzoli R, Bonjour JP, Bourrin S, Meyer JM, Vassalli P, Garcia I (1997) Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J Clin Invest 99:1699–1703

    PubMed  CAS  Google Scholar 

  • Armbrecht HJ (1990) Effect of age on calcium and phosphate absorption. Role of 1,25-dihydroxyvitamin D. Miner Electrolyte Metab 16:159–166

    PubMed  CAS  Google Scholar 

  • Armbrecht HJ, Boltz MA (1991) Expression of 25-hydroxyvitamin D 24-hydroxylase cytochrome P450 in kidney and intestine. Effect of 1,25-dihydroxyvitamin D and age. FEBS Lett 292:17–20

    PubMed  CAS  Google Scholar 

  • Armbrecht HJ, Boltz MA, Kumar VB (1999) Intestinal plasma membrane calcium pump protein and its induction by 1,25(OH)(2)D(3) decrease with age. Am J Physiol 277:41–47

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Balogh GA, de Boland AR (1999) 1,25-Dihydroxy-vitamin D3 (calcitriol)-dependent protein phosphorylation in rat duodenum: effects of ageing. Exp Gerontol 34:983–996

    PubMed  CAS  Google Scholar 

  • Balogh G, Boland R, de Boland AR (2000) l,25(OH)(2)-vitamin D(3) affects the subcellular distribution of protein kinase C isoenzymes in rat duodenum: influence of aging. J Cell Biochem 79:686–694

    PubMed  CAS  Google Scholar 

  • Banfi A, Muraglia A, Dozin B, Mastrogiacomo M, Cancedda R, Quarto R (2000) Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: implications for their use in cell therapy. Exp Hematol 28:707–715

    PubMed  CAS  Google Scholar 

  • Battmann A, Jundt G, Schulz A (1997) Endosteal human bone cells (EBC) show age-related activity in vitro. Exp Clin Endocrinol Diabetes 105:98–102

    PubMed  CAS  Google Scholar 

  • Battmann A, Schulz A, Stahl U (2001) Zelluläre Seneszenz — ein Mechanismus der Osteoporoseentstehung? Der Orthopäde 30:405–411

    PubMed  CAS  Google Scholar 

  • Beardsworth LJ, Eyre DR, Dickson IR (1990) Changes with age in the urinary excretion of lysyl-and hydroxylysylpyridinoline, two new markers of bone collagen turnover. I Bone Miner Res 5:671–676

    CAS  Google Scholar 

  • Bennett JH, Joyner CJ, Triffitt JT, Owen ME (1991) Adipocytic cells cultured from marrow have osteogenic potential. J Cell Sci 99:131–139

    PubMed  Google Scholar 

  • Beresford JN, Bennett JH, Devlin C, Leboy PS, Owen ME (1992) Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci 102:341–351

    PubMed  CAS  Google Scholar 

  • Bergman RJ, Gazit D, Kahn AJ, Gruber H, McDougall S, Hahn TJ (1996) Age-related changes in osteogenic stem cells in mice. J Bone Miner Res 11:568–577

    PubMed  CAS  Google Scholar 

  • Berkner K (2000) The vitamin K-dependent carboxylase. J Nutr 130:1877–1880

    PubMed  CAS  Google Scholar 

  • Bianco P, Robey PG (1999) Diseases of bone and the stromal cell lineage. J Bone Miner Res 14:336–341

    PubMed  CAS  Google Scholar 

  • Bianco P, Robey PG (2001) Stem cells in tissue engineering. Nature 414:118–121

    PubMed  CAS  Google Scholar 

  • Boer de J, Andressoo JO, Wit de J, Huijmans J, Beems RB, Steeg van H, Weeda G, et al (2002) Premature aging in mice deficient in DNA repair and transcription. Science 296:1276–1279

    Google Scholar 

  • Bryant RJ, Cadogan J, Weaver CM (1999) The new dietary reference intakes for calcium: implications for osteoporosis. J Am Coll Nutr 18(Suppl 5):406–412

    Google Scholar 

  • Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, et al (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260–1268

    PubMed  CAS  Google Scholar 

  • Bushinsky DA (2001) Acid-base imbalance and the skeleton. Eur J Nutr 40:238–344

    PubMed  CAS  Google Scholar 

  • Campisi J (2001) From cells to organisms: can we learn about aging from cells in culture? Exp Gerontol 36:607–618

    PubMed  CAS  Google Scholar 

  • Carmeli E, Coleman R, Reznick AZ (2002) The biochemistry of aging muscle. Exp Gerontol 37:477–489

    PubMed  CAS  Google Scholar 

  • Chan GK, Duque G (2002) Age-related bone loss: old bone, new facts. Gerontology 48:62–71

    PubMed  Google Scholar 

  • Chavassieux PM, Chenu C, Valentin-Opran A, Merle B, Delmas PD, Hartmann DJ, Saez S, et al (1990) Influence of experimental conditions on osteoblast activity in human primary bone cell cultures. J Bone Miner Res 5:337–343

    PubMed  CAS  Google Scholar 

  • Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767

    PubMed  Google Scholar 

  • Dawson-Hughes B (1998) Vitamin D and calcium: recommended intake for bone health. Osteoporos Int (Suppl) 8:30–34

    Google Scholar 

  • Delmas PD (2002) Treatment of postmenopausal osteoporosis. Lancet 359:2018–2026

    PubMed  CAS  Google Scholar 

  • DiMeglio LA, Econs MJ (2001) Hypophosphatemic rickets. Rev Endocr Metab Disord 2:165–173

    PubMed  CAS  Google Scholar 

  • Dhore CR, Cleutjens JP, Lutgens E, Cleutjens KB, Geusens PP, Kitslaar PJ, Tordoir JH, et al (2001) Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 21:1998–2003

    PubMed  CAS  Google Scholar 

  • Dreher I, Schutze N, Baur A, Hesse K, Schneider D, Kohrle J, Jakob F (1998) Selenoproteins are expressed in fetal human osteoblast-like cells. Biochem Biophys Res Commun 245:101–107

    PubMed  CAS  Google Scholar 

  • Drewnowski A, Shultz JM (2001) Impact of aging on eating behaviors, food choices, nutrition, and health status. J Nutr Health Aging 5:75–79

    PubMed  CAS  Google Scholar 

  • Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, et al (1996) Increased bone formation in osteo-calcin-deficient mice. Nature 382:448–452

    PubMed  CAS  Google Scholar 

  • Ebert-Dumig R, Schutze N, Jakob F (1999) The thioredoxin reductase/thioredoxin system in cells of the monocyte/ macrophage pathway of differentiation. Biofactors 10:227–235

    PubMed  CAS  Google Scholar 

  • Ecarot B, Desbarats M (1999) 1,25-(OH)2D3 down-regulates expression of phex, a marker of the mature osteoblast. Endocrinology 140:1192–1199

    PubMed  CAS  Google Scholar 

  • Eastell R, Simmons PS, Colwell A, Assiri AM, Burritt MF, Russell RG, Riggs BL (1992) Nyctohemeral changes in bone turnover assessed by serum bone gla-protein concentration and urinary deoxypyridinoline excretion: effects of growth and ageing. Clin Sci 83:375–382

    PubMed  CAS  Google Scholar 

  • Eastell R, Delmas PD, Hodgson SF, Eriksen EF, Mann KG, Riggs BL (1998) Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers. J Clin Endocrinol Metab 67:741–748

    Google Scholar 

  • Egrise D, Vienne A, Martin D, Schoutens A (1996) Trabecular bone cell proliferation ex vivo increases with donor age in the rat: it is correlated with the extent of bone loss and not with histomorphometric indices of bone formation. Calcif Tissue Int 59:45–50

    PubMed  CAS  Google Scholar 

  • Erben RG, Soegiarto DW, Weber K, Zeitz U, Lieberherr M, Gniadecki R, Moller G, et al (2002) Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Mol Endocrinol 16:1524–1537

    PubMed  CAS  Google Scholar 

  • Eriksen EF, Glerup H (2002) Vitamin D deficiency and aging: implications for general health and osteoporosis. Biogerontology 3:73–77

    PubMed  CAS  Google Scholar 

  • Fedarko NS, Vetter UK, Weinstein S, Robey PG (1992) Agerelated changes in hyaluronan, proteoglycan, collagen, and osteonectin synthesis by human bone cells. J Cell Physiol 151:215–227

    PubMed  CAS  Google Scholar 

  • Fedarko NS, Vetter UK, Robey PG (1995) Age-related changes in bone matrix structure in vitro. Calcif Tissue Int 56(Suppl 1):41–43

    Google Scholar 

  • Francis RM (2001) Falls and fractures. Age Ageing 30(Suppl 4):25–28

    PubMed  Google Scholar 

  • Friedman PA (2000) Mechanisms of renal calcium transport. Exp Nephrol 8:343–350

    PubMed  CAS  Google Scholar 

  • Foote JA, Giuliano AR, Harris RB (2000) Older adults need guidance to meet nutritional recommendations. J Am Coll Nutr 19:628–640

    PubMed  CAS  Google Scholar 

  • Garnero P, Delmas PD (1993) Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrinol Metab 77:1046–1053

    PubMed  CAS  Google Scholar 

  • Garnero P, Delmas PD (1996) New developments in biochemical markers for osteoporosis. Calcif Tissue Int 59 (Suppl l):2–9

    Google Scholar 

  • Gimble JM, Robinson CE, Wu X, Kelly KA, Rodriguez BR, Kliewer SA, Lehmann JM, et al (1996a) Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells. Mol Pharmacol 50:1087–1094

    PubMed  CAS  Google Scholar 

  • Gimble JM, Robinson CE, Wu X, Kelly KA (1996b) The function of adipocytes in the bone marrow stroma: an update. Bone 19:421–428

    PubMed  CAS  Google Scholar 

  • Glowacki J (1995) Influence of age on human marrow. Calcif Tissue Int 56(Suppl l):50–51

    Google Scholar 

  • Gueguen L, Pointillart A (2000) The bioavailability of dietary calcium. J Am Coll Nutr 19 (Suppl): 119–136

    Google Scholar 

  • Haden ST, Brown EM, Hurwitz S, Scott J, El-Hajj Fuleihan G (2000) The effects of age and gender on parathyroid hormone dynamics. Clin Endocrinol 52:329–338

    CAS  Google Scholar 

  • Heaney RP (2001) Constructive interactions among nutrients and bone-active pharmacologic agents with principal emphasis on calcium, phosphorus, vitamin D and protein. J Am Coll Nutr 20 (Suppl):403–409

    Google Scholar 

  • Hof van’t RJ, Ralston SH (2001) Nitric oxide and bone. Immunology 103:255–261

    Google Scholar 

  • Holick MF, Shao Q, Liu WW, Chen TC (1992) The vitamin D content of fortified milk and infant formula. N Engl J Med 326:1178–1181

    PubMed  CAS  Google Scholar 

  • Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GE, et al (1992) Hypervitaminosis D associated with drinking milk. N Engl J Med 326:1173–1177

    PubMed  CAS  Google Scholar 

  • Jakob F (1999) l,25(OH)2-vitamin D3. The vitamin D hormone. Internist 40:414–430

    Google Scholar 

  • Jakob F (2002) Vitamin D. In: Biesalski HK, Köhrle J, Schümann K (Hrsg) Vitamine, Spurenelemente und Mineralstoffe. Thieme, Stuttgart, S 21–32

    Google Scholar 

  • Jakob F (2002) Vitamin K. In: Biesalski HK, Köhrle J, Schümann K (Hrsg) Vitamine, Spurenelemente und Mineralstoffe. Thieme, Stuttgart, S 33–40

    Google Scholar 

  • Jakob F, Becker K, Paar E, Ebert-Duemig R, Schutze N (2002) Expression and regulation of thioredoxin reductases and other selenoproteins in bone. Methods Enzymol 347:168

    PubMed  CAS  Google Scholar 

  • Janssen JA, Burger H, Stolk RP, Grobbee DE, de Jong FH, Lamberts SW, Pols HA (1998) Gender-specific relationship between serum free and total IGF-I and bone mineral density in elderly men and women. Eur J Endocrinol 138:627–632

    PubMed  CAS  Google Scholar 

  • Jilka RL, Weinstein RS, Takahashi K, Parfitt AM, Manolagas SC (1996) Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence. J Clin Invest 97:1732–1740

    PubMed  CAS  Google Scholar 

  • Jilka RL, Weinstein RS, Bellido T, Parfitt AM, Manolagas SC (1998) Osteoblast programmed cell death (apoptosis): modulation by growth factors and cytokines. J Bone Miner Res 13:793–802

    PubMed  CAS  Google Scholar 

  • Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104:439–446

    PubMed  CAS  Google Scholar 

  • Johansson C, Black D, Johnell O, Odén A, Mellström D (1998) Bone mineral density is a predictor of survival. Calcif Tissue Int 63:190–196

    PubMed  CAS  Google Scholar 

  • Johnson JA, Beckman MJ, Pansini-Porta A, Christakos S, Bruns ME, Beitz DC, Horst RL, et al (1995) Age and gender effects on 1,25-dihydroxyvitamin D3-regulated gene expression. Exp Gerontol 30:631–643

    PubMed  CAS  Google Scholar 

  • Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2:165–171

    PubMed  CAS  Google Scholar 

  • Justesen J, Stenderup K, Eriksen EF, Kassem M (2002) Maintenance of osteoblastic and adipocytic differentiation potential with age and osteoporosis in human marrow stromal cell cultures. Calcif Tissue Int 71:36–44

    PubMed  CAS  Google Scholar 

  • Kahn A, Gibbons R, Perkins S, Gazit D (1995) Age-related bone loss. A hypothesis and initial assessment in mice. Clin Orthop 313:69–75

    PubMed  Google Scholar 

  • Kajkenova O, Lecka-Czernik B, Gubrij I, Hauser SP, Takahashi K, Parfitt AM, Jilka RL, et al (1997) Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia. J Bone Miner Res 12:1772–1779

    PubMed  CAS  Google Scholar 

  • Kalu DN (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175–191

    PubMed  CAS  Google Scholar 

  • Kalu DN, Chen C (1999) Ovariectomized murine model of postmenopausal calcium malabsorption. J Bone Miner Res 14:593–601

    PubMed  CAS  Google Scholar 

  • Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359:1929–1936

    PubMed  Google Scholar 

  • Keane EM, Healy M, O’Moore R, Coakley D, Walsh JB (1998) Vitamin D-fortified liquid milk: benefits for the elderly community based population. Calcif Tissue Int 62:300–302

    PubMed  CAS  Google Scholar 

  • Khosla S, Melton LJ 3rd, Riggs BL (2002a) Clinical review 144: estrogen and the male skeleton. J Clin Endocrinol Metab 87:1443–1450

    PubMed  CAS  Google Scholar 

  • Khosla S, Arrighi HM, Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Dunstan C, Riggs BL (2002b) Correlates of osteoprotegerin levels in women and men. Osteoporos Int 13:394–399

    PubMed  CAS  Google Scholar 

  • Kimble RB, Vannice JL, Bloedow DC, Thompson RC, Hopfer W, Kung VT, Brownfield C, et al (1994) Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats. J Clin Invest 93:1959–1967

    PubMed  CAS  Google Scholar 

  • Kimble RB, Bain S, Pacifici R (1997) The functional block of TNF but not of IL-6 prevents bone loss in ovariectomized mice. J Bone Miner Res 12:935–941

    PubMed  CAS  Google Scholar 

  • Kitamura H, Kawata H, Takahashi F, Higuchi Y, Furuichi T, Ohkawa H (1995) Bone marrow neutrophilia and suppressed bone turnover in human interleukin-6 transgenic mice. A cellular relationship among hematopoietic cells, osteoblasts, and osteoclasts mediated by stromal cells in bone marrow. Am J Pathol 147:1682–1692

    PubMed  CAS  Google Scholar 

  • Kitazawa R, Kimble RB, Vannice JL, Kung VT, Pacifici R (1994) Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice. J Clin Invest 94:2397–2406

    PubMed  CAS  Google Scholar 

  • Kuro-0 M (2001) Disease model: human ageing. Trends Mol Med 7:179–181

    PubMed  CAS  Google Scholar 

  • Kveiborg M, Flyvbjerg A, Rattan SI, Kassem M (2000) Changes in the insulin-like growth factor-system may contribute to in vitro age-related impaired osteoblast functions. Exp Gerontol 35:1061–1074

    PubMed  CAS  Google Scholar 

  • Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501

    PubMed  CAS  Google Scholar 

  • Lipton A, Ali SM, Leitzel K, Chinchilli V, Witters L, Engle L, Holloway D, et al (2002) Serum osteoprotegerin levels in healthy controls and cancer patients. Clin Cancer Res 8:2306–2310

    PubMed  CAS  Google Scholar 

  • Long MW, Ashcraft EK, Normalle D, Mann KG (1999) Agerelated phenotypic alterations in populations of purified human bone precursor cells. J Gerontol A Biol Sci Med Sci 54:54–62

    Google Scholar 

  • Lorenzo JA, Naprta A, Rao Y, Alander C, Glaccum M, Widmer M, Gronowicz G (1998) Mice lacking the type I interleukin-1 receptor do not lose bone mass after ovariectomy. Endocrinology 139:3022–3025

    PubMed  CAS  Google Scholar 

  • Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386:78–81

    PubMed  CAS  Google Scholar 

  • Ma XH, Muzumdar R, Yang XM, Gabriely I, Berger R, Barzilai N (2002) Aging is associated with resistance to effects of leptin on fat distribution and insulin action. J Gerontol A Biol Sci Med Sci 57:225–231

    Google Scholar 

  • MacLaughlin J, Holick MF (1985) Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 76:1536–1538

    PubMed  CAS  Google Scholar 

  • Mancini L, Moradi-Bidhendi N, Brandi ML, MacIntyre I (1998) Nitric oxide superoxide and peroxynitrite modulate osteoclast activity. Biochem Biophys Res Commun 243:785–790

    PubMed  CAS  Google Scholar 

  • Manolagas SC, Kousteni S, Jilka RL (2002) Sex steroids and bone. Recent Prog Horm Res 57:385–409

    PubMed  CAS  Google Scholar 

  • Marcus R, Wong M, Heath H 3rd, Stock JL (2002) Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes in large clinical trials with fracture as an endpoint. Endocr Rev 23:16–37

    PubMed  CAS  Google Scholar 

  • Martinez ME, Medina S, Sanchez M, Campo del MT, Esbrit P, Rodrigo A, Martinez P, et al (1999a) Influence of skeletal site of origin and donor age on l,25(OH)2D3-induced response of various osteoblastic markers in human osteoblastic cells. Bone 24:203–209

    PubMed  CAS  Google Scholar 

  • Martinez ME, Campo del MT, Medina S, Sanchez M, Sanchez-Cabezudo MJ, Esbrit P, Martinez P, et al (1999b) Influence of skeletal site of origin and donor age on osteoblastic cell growth and differentiation. Calcif Tissue Int 64:280–286

    PubMed  CAS  Google Scholar 

  • Martins I, Dantas A, Guiomar S, Amorim Cruz JA (2002) Vitamin and mineral intakes in elderly. J Nutr Health Aging 6:63–65

    PubMed  CAS  Google Scholar 

  • Massheimer V, Boland R, Boland de AR (1999) In vivo treatment with calcitriol (1,25(OH)2D3) reverses age-dependent alterations of intestinal calcium uptake in rat enterocytes. Calcif Tissue Int 64:173–178

    PubMed  CAS  Google Scholar 

  • Maurin AC, Chavassieux PM, Frappart L, Delmas PD, Serre CM, Meunier PJ (2000) Influence of mature adipocytes on osteoblast proliferation in human primary cocultures. Bone 26:485–489

    PubMed  CAS  Google Scholar 

  • McCalden RW, McGeough JA, Barker MB, Court-Brown CM (1993) Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity, mineralization, and microstructure. J Bone Joint Surg Am 75:1193–1205

    PubMed  CAS  Google Scholar 

  • McCalden RW, McGeough JA, Court-Brown CM (1997) Agerelated changes in the compressive strength of cancellous bone. The relative importance of changes in density and trabecular architecture. J Bone Joint Surg Am 79:421–427

    PubMed  CAS  Google Scholar 

  • McCarthy TL, Centrella M (2001) Local IGF-I expression and bone formation. Growth Horm IGF Res 11:213–219

    PubMed  CAS  Google Scholar 

  • McKane WR, Khosla S, Egan KS, Robins SP, Burritt MF, Riggs BL (1996) Role of calcium intake in modulating age-related increases in parathyroid function and bone resorption. J Clin Endocrinol Metab 81:1699–1703

    PubMed  CAS  Google Scholar 

  • Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, et al (2000) Extension of life-span with superoxide dismutase/catalase mimetics. Science 289:1567–1569

    PubMed  CAS  Google Scholar 

  • Meunier P, Aaron J, Edouard C, Vignon G (1971) Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin Orthop 80:147–154

    PubMed  CAS  Google Scholar 

  • Meyer RA Jr, Young CG, Meyer MH, Garges PL, Price DK (2000) Effect of age on the expression of Pex (Phex) in the mouse. Calcif Tissue Int 66:282–287

    PubMed  CAS  Google Scholar 

  • Michel JJ, Scott JD (2002) AKAP mediated signal transduction. Annu Rev Pharmacol Toxicol 42:235–257

    PubMed  CAS  Google Scholar 

  • Moreno-Reyes R, Egrise D, Neve J, Pasteeis JL, Schoutens A (2001) Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia. J Bone Miner Res 16:1556–1563

    PubMed  CAS  Google Scholar 

  • Moriguti JC, Ferriolli E, Marchini JS (1999) Urinary calcium loss in elderly men on a vegetable: animal (1:1) highprotein diet. Gerontology 45:274–278

    PubMed  CAS  Google Scholar 

  • Mühlberg W, Platt D (1999) Age-dependent changes of the kidneys: pharmacological implications. Gerontology 45: 243–253

    PubMed  Google Scholar 

  • Müller SM, Glowacki J (2001) Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges. J Cell Biochem 82:583–590

    Google Scholar 

  • Mundy GR (2001) Osteoporosis: pathophysiology and nonpharmacological management. Best Pract Res Clin Rheumatol 15:727–745

    PubMed  CAS  Google Scholar 

  • Mundy GR (2002) Directions of drug discovery in osteoporosis. Annu Rev Med 53:337–354

    PubMed  CAS  Google Scholar 

  • Muraglia A, Cancedda R, Quarto R (2000) Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J Cell Sci 113:1161–1166

    PubMed  CAS  Google Scholar 

  • Muschler GF, Nitto H, Boehm CA, Easley KA (2001) Ageand gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res 19:117–125

    PubMed  CAS  Google Scholar 

  • Need AG, Horowitz M, Morris HA, Nordin BC (2000) Vitamin D status: effects on parathyroid hormone and 1,25-dihydroxyvitamin D in postmenopausal women. Am J Clin Nutr 71:1577–1581

    PubMed  CAS  Google Scholar 

  • Nimni BS, Bernick S, Paule W, Nimni ME (1993) Changes in the ratio of non-calcified collagen to calcified collagen in human vertebrae with advancing age. Connect Tissue Res 29:133–140

    PubMed  CAS  Google Scholar 

  • Nishida S, Endo N, Yamagiwa H, Tanizawa T, Takahashi HE (1999) Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation. J Bone Miner Metab 17:171–177

    PubMed  CAS  Google Scholar 

  • Nordin BE, Need AG, Steurer T, Morris HA, Chatterton BE, Horowitz M (1998) Nutrition, osteoporosis, and aging. Ann NY Acad Sci 854:336–351

    PubMed  CAS  Google Scholar 

  • North American Menopause Society (2001) The role of calcium in peri-and postmenopausal women: consensus opinion of The North American Menopause Society. Menopause 8:84–95

    Google Scholar 

  • Ohlsson C, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC (1998) Growth hormone and bone. Endocr Rev 19:55–79

    PubMed  CAS  Google Scholar 

  • Orr WC, Sohal RS (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263:1128–1130

    PubMed  CAS  Google Scholar 

  • Pacifici R (1999) Aging and cytokine production. Calcif Tissue Int 65:345–351

    PubMed  CAS  Google Scholar 

  • Pattanaungkul S, Riggs BL, Yergey AL, Vieira NE, O’Fallon WM, Khosla S (2000) Relationship of intestinal calcium absorption to 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in young versus elderly women: evidence for agerelated intestinal resistance to 1,25(OH)2D action. J Clin Endocrinol Metab 85:4023–4027

    PubMed  CAS  Google Scholar 

  • Perkins SL, Gibbons R, Kling S, Kahn AJ (1994) Age-related bone loss in mice is associated with an increased osteoclast progenitor pool. Bone 15:65–72

    PubMed  CAS  Google Scholar 

  • Perry HM 3rd, Horowitz M, Morley JE, Patrick P, Vellas B, Baumgartner R, Garry PJ (1999) Longitudinal changes in serum 25-hydroxyvitamin D in older people. Metabolism 48:1028–1032

    PubMed  CAS  Google Scholar 

  • Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C (2000) Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 15:1113–1118

    PubMed  CAS  Google Scholar 

  • Pfeilschifter J, Diel I, Pilz U, Brunotte K, Naumann A, Ziegler R (1993) Mitogenic responsiveness of human bone cells in vitro to hormones and growth factors decreases with age. J Bone Miner Res 8:707–717

    PubMed  CAS  Google Scholar 

  • Pfeilschifter J, Koditz R, Pfohl M, Schatz H (2002) Changes in proinflammatory cytokine activity after menopause. Endocr Rev 23:90–119

    PubMed  CAS  Google Scholar 

  • Poli V, Balena R, Fattori E, Markatos A, Yamamoto M, Tanaka H, Ciliberto G, et al (1994) Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. EMBO J 13:1189–1196

    PubMed  CAS  Google Scholar 

  • Portale AA, Lonergan ET, Tanney DM, Halloran BP (1997) Aging alters calcium regulation of serum concentration of parathyroid hormone in healthy men. Am J Physiol 272:139–146

    Google Scholar 

  • Price PA, June HH, Buckley JR, Williamson MK (2001) Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler Thromb Vasc Biol 21:1610–1616

    PubMed  CAS  Google Scholar 

  • Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E (2002) Protein consumption and bone mineral density in the elderly: the Rancho Bernardo Study. Am J Epidemiol 155:636–644

    PubMed  Google Scholar 

  • Quarto R, Thomas D, Liang CT (1995) Bone progenitor cell deficits and the age-associated decline in bone repair capacity. Calcif Tissue Int 56:123–139

    PubMed  CAS  Google Scholar 

  • Qiu S, Rao DS, Palnitkar S, Parfitt AM (2002) Age and distance from the surface but not menopause reduce osteocyte density in human cancellous bone. Bone 31:313–318

    PubMed  CAS  Google Scholar 

  • Ralston SH (2002) Genetic control of susceptibility to osteoporosis. J Clin Endocrinol Metab 87:2460–2466

    PubMed  CAS  Google Scholar 

  • Reginster JY, Frederick I, Deroisy R, Dewe W, Taquet AN, Albert A, Collette J, et al (1998) Parathyroid hormone plasma concentrations in response to low 25-OH vitamin D circulating levels increases with age in elderly women. Osteoporos Int 8:390–392

    PubMed  CAS  Google Scholar 

  • Robins SP, Woitge H, Hesley R, Ju J, Seyedin S, Seibel MJ (1994) Direct, enzyme-linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption. J Bone Miner Res 9:1643–1649

    PubMed  CAS  Google Scholar 

  • Roholl PJ, Blauw E, Zurcher C, Dormans JA, Theuns HM (1994) Evidence for a diminished maturation of preosteoblasts into osteoblasts during aging in rats: an ultrastructural analysis. J Bone Miner Res 9:355–366

    PubMed  CAS  Google Scholar 

  • Rosen CJ (2000) Growth hormone and aging. Endocrine 12:197–201

    PubMed  CAS  Google Scholar 

  • Russell RM (2000) The aging process as a modifier of metabolism. Am J Clin Nutr 72 (Suppl):529–532

    Google Scholar 

  • Schiavi SC, Moe OW (2002) Phosphatonins: a new class of phosphate-regulating proteins. Curr Opin Nephrol Hypertens 11:423–430

    PubMed  Google Scholar 

  • Schoppet M, Preissner KT, Hofbauer LC (2002) RANK ligand and osteoprotegerin: paraerine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 22:549–553

    PubMed  CAS  Google Scholar 

  • Schurgers LJ, Dissel PE, Spronk HM, Soute BA, Dhore CR, Cleutjens JP, Vermeer C (2001) Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol 90(Suppl 3):57–63

    PubMed  Google Scholar 

  • Schütze N, Jakob F (2001) Osteoporose. In: Ganten D, Ruckpaul K (Hrsg) Molekularmedizinische Grundlagen von Endokrinopathien. Springer, Berlin Heidelberg New York, S 137–188

    Google Scholar 

  • Schütze N, Bachthaler M, Lechner A, Kohrle J, Jakob F (1998) Identification by differential display PCR of the selenoprotein thioredoxin reductase as a 1 alpha,25(OH)2-vitamin D3-responsive gene in humanosteoblasts — regulation by selenite. Biofactors 7:299–310

    PubMed  Google Scholar 

  • Schütze N, Fritsche J, Ebert-Dumig R, Schneider D, Kohrle J, Andreesen R, Kreutz M, et al (1999) The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells — regulation by 1,25-dihydroxyvitamin D3 and selenite. Biofactors 10:329–338

    PubMed  Google Scholar 

  • Seck T, Bretz A, Krempien R, Krempien B, Ziegler R, Pfeilschifter J (1999) Age-related changes in insulin-like growth factor I and II in human femoral cortical bone: lack of correlation with bone mass. Bone 24:387–393

    PubMed  CAS  Google Scholar 

  • Seeman E (2002) Pathogenesis of bone fragility in women and men. Lancet 359:1841–1850

    PubMed  Google Scholar 

  • Seibel MJ, Woitge HW (1999) Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects. J Clin Densitom 2:299–321

    PubMed  CAS  Google Scholar 

  • Seibel MJ, Woitge H, Scheidt-Nave C, Leidig-Bruckner G, Duncan A, Nicol P, Ziegler R, et al (1994) Urinary hydroxypyridinium crosslinks of collagen in population-based screening for overt vertebral osteoporosis: results of a pilot study. J Bone Miner Res 9:1433–1440

    PubMed  CAS  Google Scholar 

  • Semba RD, Garrett E, Johnson BA, Guralnik JM, Fried LP (2000) Vitamin D deficiency among older women with and without disability. Am J Clin Nutr 72:1529–1534

    PubMed  CAS  Google Scholar 

  • Seufert J, Ebert K, Muller J, Eulert J, Hendrich C, Werner E, Schütze N, et al (2001) Octreotide therapy for tumor-induced osteomalacia. N Engl J Med 345:1883–1888

    PubMed  CAS  Google Scholar 

  • Shearer MJ (2000) Role of vitamin K and gla proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care 3:433–438

    PubMed  CAS  Google Scholar 

  • Simonsen JL, Rosada C, Serakinci N, Justesen J, Stenderup K, Rattan SI, Jensen TG, et al (2002) Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol 20:592–596

    PubMed  CAS  Google Scholar 

  • Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273:59–63

    PubMed  CAS  Google Scholar 

  • Souberbielle JC, Cormier C, Kindermans C, Gao P, Cantor T, Forette F, Baulieu EE (2001) Vitamin D status and redefining serum parathyroid hormone reference range in the elderly. J Clin Endocrinol Metab 86:3086–3090

    PubMed  CAS  Google Scholar 

  • Squier TC, Bigelow DJ (2000) Protein oxidation and age-dependent alterations in calcium homeostasis. Front Biosci 5:504–526

    Google Scholar 

  • Stein MS, Wark JD, Scherer SC, Walton SL, Chick P, Di Carlantonio M, Zajac JD, et al (1999) Falls relate to vitamin D and parathyroid hormone in an Australian nursing home and hostel. J Am Geriatr Soc 47:1195–1201

    PubMed  CAS  Google Scholar 

  • Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M (2001) Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis. J Bone Miner Res 16:1120–1129

    PubMed  CAS  Google Scholar 

  • Sun J, Folk D, Bradley TJ, Tower J (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics 161:661–672

    PubMed  CAS  Google Scholar 

  • Szulc P, Hofbauer LC, Heufelder AE, Roth S, Delmas PD (2001) Osteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone status. J Clin Endocrinol Metab 86:3162–3165

    PubMed  CAS  Google Scholar 

  • Takeda S, Karsenty G (2001) Central control of bone formation. J Bone Miner Metab 19:195–198

    PubMed  CAS  Google Scholar 

  • Tan CY, Statham B, Marks R, Payne PA (1982) Skin thickness measurement by pulsed ultrasound: its reproducibility, validation and variability. Br J Dermatol 106:657–667

    PubMed  CAS  Google Scholar 

  • Taub J, Lau JF, Ma C, Hahn JH, Hoque R, Rothblatt J, Chalfie M (1999) A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. Nature 399:162–166

    PubMed  CAS  Google Scholar 

  • Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, et al (1998) Hypovitaminosis D in medical inpatients. N Engl J Med 338:777–783

    PubMed  CAS  Google Scholar 

  • Thomas SE, Anderson S, Gordon KL, Oyama TT, Shankland SJ, Johnson RJ (1998) Tubulointerstitial disease in aging: evidence for underlying peritubular capillary damage, a potential role for renal ischemia. J Am Soc Nephrol 9:231–242

    PubMed  CAS  Google Scholar 

  • Tomkinson A, Reeve J, Shaw RW, Noble BS (1997) The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endocrinol Metab 82:3128–3135

    PubMed  CAS  Google Scholar 

  • Tsuji T, Hughes FJ, McCulloch CA, Melcher AH (1990) Effects of donor age on osteogenic cells of rat bone marrow in vitro. Mech Ageing Dev 51:121–132

    PubMed  CAS  Google Scholar 

  • Turner RT, Maran A, Lotinun S, Hefferan T, Evans GL, Zhang M, Sibonga JD (2001) Animal models for osteoporosis. Rev Endocr Metab Disord 2:117–127

    PubMed  CAS  Google Scholar 

  • Van den Heuvel R, Mathieu E, Schoeters G, Leppens H, Vanderborght O (1991) Stromal cells from murine developing hemopoietic organs: comparison of colony-forming unit of fibroblasts and long-term cultures. Int J Dev Biol 35:33–41

    PubMed  Google Scholar 

  • Van Voorhies WA, Ward S (1999) Long-lived Caenorhabditis elegans mutants have reduced metabolic rates. Proc Natl Acad Sci USA 96:11399–11403

    PubMed  Google Scholar 

  • Vieth R (1999) Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 69:842–856

    PubMed  CAS  Google Scholar 

  • Wang L, Banu J, McMahan CA, Kalu DN (2001) Male rodent model of age-related bone loss in men. Bone 29:141–148

    PubMed  CAS  Google Scholar 

  • Wong MM, Rao LG, Ly H, Hamilton L, Ish-Shalom S, Sturtridge W, Tong J, et al (1994) In vitro study of osteoblastic cells from patients with idiopathic osteoporosis and comparison with cells from non-osteoporotic controls. Osteoporos Int 4:21–31

    PubMed  CAS  Google Scholar 

  • Zittermann A (2001) Effects of vitamin K on calcium and bone metabolism. Curr Opin Clin Nutr Metab Care 4: 483–487

    PubMed  CAS  Google Scholar 

  • Zoidis E, Zapf J, Schmid C (2000) Phex cDNA cloning from rat bone and studies on phex mRNA expression: tissuespecificity, age-dependency, and regulation by insulinlike growth factor (IGF) I in vivo. Mol Cell Endocrinol 168:41–51

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Franz Jakob
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norbert Schütze
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13122, Berlin-Buch, Germany

    Detlev Ganten  & Klaus Ruckpaul  & 

  2. Instituto Universitario de Investigación Gerontológica, Diego de León 62, E-28006, Madrid, Germany

    Antonio Ruiz-Torres

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Jakob, F., Schütze, N. (2004). Molekulare Mechanismen altersspezifischer Veränderungen des Kalzium- und Knochenstoffwechsels. In: Ganten, D., Ruckpaul, K., Ruiz-Torres, A. (eds) Molekularmedizinische Grundlagen von altersspezifischen Erkrankungen. Molekulare Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18741-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-18741-4_13

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62272-4

  • Online ISBN: 978-3-642-18741-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation