Top

Osteoporosis International

Published in:

01-08-2009 | Personal View

Thinking inside and outside the envelopes of bone

Dedicated to PDD

Authors: P. Szulc, E. Seeman

Published in: Osteoporosis International | Issue 8/2009

Abstract

Introduction

Bone modeling and remodeling is the final common pathway expressing all genetic and environmental factors that influence the attainment and maintenance of bone’s material and structural strength. Modeling and remodeling require a surface, and during growth this cellular machinery fashions bone’s external size, shape, and internal architecture by depositing bone on, and removing bone from, both its periosteal (external) and endosteal (internal) envelopes. Bone is distributed and redistributed to achieve strength commensurate with its loading requirements.

Methods

Advancing age is associated with: (1) a reduction in the volume of bone resorbed by each basic multicellular unit (BMU); (2) an even greater reduction in the volume of bone formed by each BMU so that each remodeling event, whether adaptive or reparative, removes bone from the bone; (3) increased remodeling (number of BMUs) on the three (endocortical, intracortical, and trabecular) components of its endosteal envelope in midlife in women and late in life in both sexes; and (4) reduced bone formation on the periosteal envelope. The net effect is cortical thinning, increased intracortical porosity, trabecular thinning, and loss of connectivity.

Results

While remodeling intensity on an envelope determines structure (e.g., trabecular perforations), the surface area of the envelope determines remodeling intensity, and, so, structure. High remodeling on trabecular surfaces decreases as trabeculae (with their surface) are lost. Conversely, remodeling on the endocortical and intracortical envelopes increases their surface area, so remodeling intensity increases and bone loss becomes predominantly cortical.

Conclusions

Understanding bone structural strength and its decay and the effects of genetic factors, exercise, nutrition, and drug therapy on bone requires thinking outside and inside these envelopes; their absolute and relative movements during growth and aging determine bone structure and its strength.

Currey J (2002) Bones. Structure and mechanics. Princeton UP, Princeton, pp 1–380

Parfitt AM (1996) Skeletal heterogeneity and the purposes of bone remodelling: implications for the understanding of osteoporosis. In: Marcus R, Feldman D, Kelsey J (eds) Osteoporosis. Academic, San Diego, pp 315–339

Haapasalo H, Kontulainen S, Sievanen H, Kannus P, Jarvinen M, Vuori I (2000) Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: a peripheral quantitative computed tomography study of the upper arms of male tennis players. Bone 27:351–357PubMedCrossRef

Murray PDF, Huxley JS (1925) Self differentiation in the grafted limb bud of the chick. J Anat 59:379–384PubMed

Hattner R, Epker BN, Frost HM (1965) Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling. Nature 206:489–490PubMedCrossRef

Rauch F, Neu C, Manz F, Schoenau E (2001) The development of metaphyseal cortex—implications for distal radius fractures during growth. J Bone Miner Res 16:1547–1555PubMedCrossRef

Orwoll ES (2003) Toward an expanded understanding of the role of the periosteum in skeletal health. J Bone Miner Res 18:949–954PubMedCrossRef

Parfitt AM (2002) Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone 30:5–7PubMedCrossRef

Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15:613–620PubMedCrossRef

10.

Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY (2005) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294–1301PubMedCrossRef

11.

Parfitt AM (2001) The bone remodeling compartment: a circulatory function for bone lining cells. J Bone Miner Res 16:1583–1585PubMedCrossRef

12.

Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F (2001) Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res 16:1575–1582PubMedCrossRef

13.

Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261PubMedCrossRef

14.

SPRA AF (1941) Postmenopausal osteoporosis. J Am Med Assoc 116:2465–2474

15.

Lips P, Courpron P, Meunier PJ (1978) Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age. Calcif Tissue Res 26:13–17PubMedCrossRef

16.

Vedi S, Compston JE, Webb A, Tighe JR (1982) Histomorphometric analysis of bone biopsies from the iliac crest of normal British subjects. Metab Bone Dis Relat Res 4:231–236PubMedCrossRef

17.

Bonyadi M, Waldman SD, Liu D, Aubin JE, Grynpas MD, Stanford WL (2003) Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice. Proc Natl Acad Sci U S A 100:5840–5845PubMedCrossRef

18.

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 17:171–177PubMedCrossRef

19.

Oreffo RO, Bord S, Triffitt JT (1998) Skeletal progenitor cells and ageing human populations. Clin Sci (Lond) 94:549–555

20.

Eriksen EF (1986) Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Endocr Rev 7:379–408PubMedCrossRef

21.

Eriksen EF, Langdahl B, Vesterby A, Rungby J, Kassem M (1999) Hormone replacement therapy prevents osteoclastic hyperactivity: a histomorphometric study in early postmenopausal women. J Bone Miner Res 14:1217–1221PubMedCrossRef

22.

Compston JE, Yamaguchi K, Croucher PI, Garrahan NJ, Lindsay PC, Shaw RW (1995) The effects of gonadotrophin-releasing hormone agonists on iliac crest cancellous bone structure in women with endometriosis. Bone 16:261–267PubMedCrossRef

23.

Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21:115–137PubMedCrossRef

24.

Eriksen EF, Mosekilde L, Melsen F (1985) Trabecular bone resorption depth decreases with age: differences between normal males and females. Bone 6:141–146PubMedCrossRef

25.

Cohen-Solal ME, Shih MS, Lundy MW, Parfitt AM (1991) A new method for measuring cancellous bone erosion depth: application to the cellular mechanisms of bone loss in postmenopausal women. J Bone Miner Res 6:1331–1338PubMedCrossRef

26.

Birkenhäger-Frenkel DH, Nigg AL, Hens CJJ, Birkenhäger JC (1993) Changes of interstitial bone thickness with age in men and women. Bone 14:211–216PubMedCrossRef

27.

Croucher PI, Mellish RWE, Vedi S, Garrahan NJ, Compston JE (1989) The relationship between resorption depth and mean interstitial bone thickness: age-related changes in man. Calcif Tissue Int 45:15–19PubMedCrossRef

28.

Balena R, Shih MS, Parfitt AM (1992) Bone resorption and formation on the periosteal envelope of the ilium: a histomorphometric study in healthy women. J Bone Miner Res 7:1475–1482PubMedCrossRef

29.

Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S (2004) Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res 19:1945–1954PubMedCrossRef

30.

Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L, Amin S, Rouleau PA, Khosla S (2008) A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res 23:205–214PubMedCrossRef

31.

Riggs BL, Wahner HW, Melton LJ 3rd, Richelson LS, Judd HL, Offord KP (1986) Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause. J Clin Invest 77:1487–1491PubMedCrossRef

32.

Gilsanz V, Gibbens DT, Carlson M, Boechat MI, Cann CE, Schulz EE (1988) Peak trabecular vertebral density: a comparison of adolescent and adult females. Calcif Tissue Int 43:260–262PubMedCrossRef

33.

van der Linden JC, Homminga J, Verhaar JA, Weinans H (2001) Mechanical consequences of bone loss in cancellous bone. J Bone Miner Res 16:457–465PubMedCrossRef

34.

Seeman E (2003) Periosteal bone formation—a neglected determinant of bone strength. N Engl J Med 349:320–323PubMedCrossRef

35.

Szulc P, Seeman E, Duboeuf F, Sornay-Rendu E, Delmas PD (2006) Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J Bone Miner Res 21:1856–1863PubMedCrossRef

36.

Parfitt A (1980) Morphological basis of bone mineral measurements: transient and steady state effects of treatment in osteoporosis. Miner Electrolyte Metab 4:273–287

37.

Akkus O, Polyakova-Akkus A, Adar F, Schaffler MB (2003) Aging of microstructural compartments in human compact bone. J Bone Miner Res 18:1012–1019PubMedCrossRef

38.

Parfitt AM (1984) The cellular basis of bone remodeling: the quantum concept reexamined in light of recent advances in the cell biology of bone. Calcif Tissue Int 36(Suppl 1):S37–S45PubMedCrossRef

39.

Brown JP, Delmas PD, Arlot M, Meunier PJ (1987) Active bone turnover of the cortico-endosteal envelope in postmenopausal osteoporosis. J Clin Endocrinol Metab 6:954–959CrossRef

40.

Arlot ME, Delmas PD, Chappard D, Meunier PJ (1990) Trabecular and endocortical bone remodeling in postmenopausal osteoporosis: comparison with normal postmenopausal women. Osteoporos Int 1:41–49PubMedCrossRef

41.

Foldes J, Parfitt AM, Shih MS, Rao DS, Kleerekoper M (1991) Structural and geometric changes in iliac bone: relationship to normal aging and osteoporosis. J Bone Miner Res 6:759–766PubMed

42.

Martin RB (1984) Porosity and specific surface of bone. Crit Rev Biomed Eng 10:179–222PubMed

43.

Brockstedt H, Kassem M, Eriksen EF, Mosekilde L, Melsen F (1993) Age- and sex-related changes in iliac cortical bone mass and remodeling. Bone 14:681–691PubMedCrossRef

44.

Yeni YN, Brown CU, Wang Z, Norman TL (1997) The influence of bone morphology on fracture toughness of the human femur and tibia. Bone 21:453–459PubMedCrossRef

45.

Hernandez CJ, Gupta A, Keaveny TM (2006) A biomechanical analysis of the effects of resorption cavities on cancellous bone strength. J Bone Miner Res 21:1248–1255PubMedCrossRef

46.

Boivin G, Lips P, Ott SM, Harper KD, Sarkar S, Pinette KV, Meunier PJ (2003) Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. J Clin Endocrinol Metab 88:4199–4205PubMedCrossRef

47.

Boivin G, Meunier PJ (2002) Changes in bone remodeling rate influence the degree of mineralization of bone. Connect Tissue Res 43:535–537PubMedCrossRef

48.

Viguet-Carrin S, Garnero P, Delmas PD (2006) The role of collagen in bone strength. Osteoporos Int 17:319–336PubMedCrossRef

49.

Garnero P, Borel O, Gineyts E, Duboeuf F, Solberg H, Bouxsein ML, Christiansen C, Delmas PD (2006) Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone 38:300–309PubMedCrossRef

50.

Bailey AJ, Sims TJ, Ebbesen EN, Mansell JP, Thomsen JS, Mosekilde L (1999) Age-related changes in the biochemical properties of human cancellous bone collagen: relationship to bone strength. Calcif Tissue Int 65:203–210PubMedCrossRef

51.

Banse X, Sims TJ, Bailey AJ (2002) Mechanical properties of adult vertebral cancellous bone: correlation with collagen intermolecular cross-links. J Bone Miner Res 17:1621–1628PubMedCrossRef

52.

Nalla RK, Kruzic JJ, Kinney JH, Ritchie RO (2004) Effect of aging on the toughness of human cortical bone: evaluation by R-curves. Bone 35:1240–1246PubMedCrossRef

53.

Qiu S, Rao DS, Fyhrie DP, Palnitkar S, Parfitt AM (2005) The morphological association between microcracks and osteocyte lacunae in human cortical bone. Bone 37:10–15PubMedCrossRef

54.

Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK (2003) Bone loss and bone size after menopause. N Engl J Med 349:327–334PubMedCrossRef

55.

Aaron JE, Makins NB, Sagreiya K (1987) The microanatomy of trabecular bone loss in normal aging men and women. Clin Orthop Relat Res 215:260–271PubMed

56.

Duan Y, Beck TJ, Wang XF, Seeman E (2003) Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J Bone Miner Res 18(10):1766–1774PubMedCrossRef

57.

Duan Y, Turner CH, Kim BT, Seeman E (2001) Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than bone loss. J Bone Miner Res 16:2267–2275PubMedCrossRef

58.

Duan Y, Wang XF, Evans A, Seeman E (2005) Structural and biomechanical basis of racial and sex differences in vertebral fragility in Chinese and Caucasians. Bone 36:987–998PubMedCrossRef

59.

Wang XF, Duan Y, Beck TJ, Seeman E (2005) Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone 36:978–986PubMedCrossRef

60.

Seeman E, Duan Y, Fong C, Edmonds J (2001) Fracture site-specific deficits in bone size and volumetric density in men with spine or hip fractures. J Bone Miner Res 16:120–127PubMedCrossRef

Title: Thinking inside and outside the envelopes of bone
Dedicated to PDD
Authors: P. Szulc
E. Seeman
Publication date: 01-08-2009
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 8/2009
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-009-0994-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Thinking inside and outside the envelopes of bone

Dedicated to PDD

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 8/2009

Differences in persistence among different weekly oral bisphosphonate medications

Effects of bone anabolic agents on bone ultrastructure

Targeted exercises against hip fragility

The incidence and risk of hip fracture in Poland

Teriparatide in men: persistence and geographical variation in the UK

Bone microdamage: a clinical perspective