Summary
The most plausible purpose for bone remodeling is to prevent excessive aging of bone, which can cause osteocyte death and increase susceptibility to fatigue microdamage. The age of any particular volume of bone depends on two factors: the probability of remodeling beginning on the nearest bone surface, which is given by the local activation frequency; and the probability of a particular remodeling event penetrating to a specified distance from the surface. These two probabilities can be combined in a mathematical model. According to the model, within about 40 μm from the surface, the rate of surface remodeling is the main determinant of bone age, but beyond 40 μm, the distance from the surface becomes progressively more important. Beyond 75 μm, the bone is essentially isolated from surface remodeling. Application of the model to subjects with and without vertebral fracture indicated that the proportion of iliac cancellous bone with a mean age greater than 20 years was less than 20% in all the control subjects without fracture, but was more than 20% in about one-third of the patients with fracture. Bone age is a major determinant of the degree of mineralization, so that osteoporotic patients with prolonged bone age should have bone of higher true mineral density. Accordingly, mineral density distribution was determined by scanning electron microscopy with backscattered electron imaging, calibrated in terms of atomic number. In osteoporotic patients, the mean atomic number was lower, the proportion of bone with high values was lower, and the proportion of bone with low values was higher than in control subjects, the opposite of what would be predicted by the bone age model just described. These data, together with our failure, to date, to detect osteocyte death and fatigue microdamage in iliac cancellous bone in patients with osteoporosis, cast doubt on the role of low bone turnover and increased bone age in the pathogenesis of vertebral fracture. Although conclusive data are still lacking, bone age, osteocyte death, and fatigue failure are more likely relevant to the pathogenesis of hip fracture. Nevertheless, enhanced bone conservation as a result of modest therapeutic inhibition of remodeling activation more than offsets the hypothetical risk of increasing bone age.
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References
Parfitt AM (1990) Pharmacologic manipulation of bone remodelling and calcium homeostasis. In: Kanis JA (ed) Progress in basic and clinical pharmacology, vol. 4. Calcium metabolism. S Karger, Basel pp 1–27
Frost HM (1986) Intermediary organization of the skeleton. CRC Press, Boca Raton
Parfitt AM (1990) Bone-forming cells in clinical conditions. In: Hall BK (ed) Bone: a treatise, vol 1. The osteoblast and osteocyte. Telford Press, Caldwell (NJ), pp 351–429
Frost HM (1985) In vivo osteocyte death. J Bone Joint Surg 42-A:138–143
Frost HM (1985) The pathomechanics of osteoporoses. Clin Orthop 200:198–225
Carter DR, Cater WE (1985) A cumulative damage model for bone fracture. J Orthop Res 3:84–90
Parfitt AM (1988) The composition, structure and remodeling of bone: a basis for the interpretation of bone mineral measurements. In: Dequeker J, Geusens P, Wahner HW (eds). Bone mineral measurements by photon absorptiometry: methodological problems. Leuven University Press, Leuven, pp 9–28
Grynpas MD (1993) Age- and disease-related changes in the mineral of bone. Calcif Tissue Int 53(Suppl. 1):57–64
Frost HM (1960) Micropetrosis. J Bone Joint Surg 42-A:144–150
Lanyon L (1993) Osteocytes, strain detection, and remodeling. Calcif Tissue Int 53(Suppl. 1):102–107
Foldes J, Parfitt AM, Shih M-S, Rao DS, Kleerekoper M (1991) Structural and geometric changes in iliac bone: relationship to normal aging and osteoporosis. J Bone Miner Res 6:759–766
Parfitt AM, Mathews C, Rao D, Frame B, Kleerekoper M, Villanueva AR (1981) Impaired osteoblast function in metabolic bone disease. In: DeLuca HF, Frost H, Jee W, Johnston C, Parfitt AM (eds) Osteoporosis: recent advances in pathogenesis and treatment. University Park Press, Baltimore, pp 321–330
Parfitt AM, Kleerekoper M (1984) Diagnostic value of bone histomorphometry and comparison of histologic measurements and biochemical indices of bone remodeling. In: Christiansen C, Arnaud CD, Nordin BEC, Parfitt AM, Peck WA, Riggs BL (eds) Osteoporosis. Proc Copenhagen International Symposium on Osteoporosis, June 3–8, 1984. Aalborg Stiftsbogtrykkeri, pp 111–120
Hattner R, Frost HM (1963) Mean skeletal age: its calculation, and theoretical effects on skeletal trace physiology and on the physical characteristics of bone. Henry Ford Hosp Med Bull 11:201–216
Parfitt AM (1987) Pathogenesis of vertebral fracture: qualitative abnormalities in bone architecture and bone age. In: Roche AF (ed) Osteoporosis: current concepts. Report of the 7th Ross Conference on Medical Research. Ross Laboratories, Columbus, Ohio, pp 18–22
Parfitt AM, Kleerekoper M, Villanueva AR (1987) Increased bone age: mechanisms and consequences. In: Christiansen C, Johansen C, Riis BJ (eds) Osteoporosis 1987. Osteopress ApS, Copenhagen, pp 301–308
Kleerekoper M, Villanueva AR, Stanciu J, Rao DS, Parfitt AM (1985) The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif Tissue Int 37:594–597
Parfitt AM (1992) The two-stage concept of bone loss revisited. Triangle 31:99–110
Cohen-Solal M, Shih M-S, Lundy MW, Parfitt AM (1991) A new method for measuring cancellous bone erosion depth: application to the cellular mechanisms of bone loss in post-menopausal osteoporosis. J Bone Miner Res 6:1331–1338
Lacroix P (1991) The internal remodeling of bones. In: Bourne GH (ed) The biochemistry and physiology of bone, 2nd ed. Academic Press, New York, pp 119–144
Obrant KJ, Odselius R (1984) Electron microprobe analysis and histochemical examination of the calcium distribution in human bone trabeculae: a methodological study using biopsy specimens from posttraumatic osteopenia. Ultrastruct Pathol 7:123–131
Dickenson RP, Hutton WC, Stott JRR (1981) The mechanical properties of bone in osteoporosis. J Bone Joint Surg 63-B:233–238
Lundy MW, Riddle JM, Pitchford WC, Parfitt AM (in press) Mineral content and distribution in normal and osteoporotic subjects studied by backscattered electron imaging. Scanning Microsc Int
Burnell JM, Baylink DJ, Chesnut CH, Mathews MW, Teubner EJ (1982) Bone matrix and mineral abnormalities in postmenopausal osteoporosis. Metabolism 31:1113–1120
Flora L, Hassing GS, Parfitt AM, Villanueva AR (1981) Comparative skeletal effects of two diphosphonates in dogs. In: Jee WSS, Parfitt AM (eds) Bone histomorphometry: 3rd International Workshop. Paris, Armour-Montagu, pp 389–407
Tamayo R, Goldman J, Villanueva A, Walczak N, Whitehouse F, Parfitt AM (1981) Bone mass and bone cell function in diabetes. Diabetes 20(suppl 1):31A
Parfitt AM (1988) Idiopathic, surgical and other varieties of parathyroid hormone-deficient hypoparathyroidism. In: DeGroot L (ed) Metabolic basis of endocrinology, 2nd ed. Grune and Stratton, New York, pp 1049–1064
Heath H, Melton LJ, Chu C-P (1980) Diabetes mellitus and the risk of skeletal fracture. N Engl J Med 303:567–570
Seeman E, Wahner HW, Offerek TP, Kumar R, Johnson WJ, Riggs BC (1982) Differential effects of endocrine dysfunction on the axial and the appendicular skeleton. J Clin Invest 69:1302–1309
Melsen F, Mosekilde Le, Eriksen EF, Charles P, Steinicke T (1989) In vivo hormonal effects on trabecular bone remodeling, osteoid mineralization, and skeletal turnover. In: Kleerekoper M, Krane SM (eds) Clinical disorders of bone and mineral metabolism. Mary Ann Liebert, New York, pp 73–87
Nottestad SY, Baumel JJ, Kimmel DB, Recker RR, Heaney RP (1987) The proportion of trabecular bone in human vertebrae. J Bone Miner Res 2:221–229
Mazess RB (1990) Fracture risk: a role for compact bone. Calcif Tissue Int 47:191–193
Parfitt AM (1989) Surface speck bone remodeling in health and disease. In: Kleerekoper M, Krane S (eds) Clinical disorders of bone and mineral metabolism. Mary Ann Liebert, New York, pp 7–14
Ham AW (1952) Some histophysiological problems peculiar to calcified tissues. J Bone Joint Surg 34-A:701–728
Eventov I, Frisch B, Cohen Z, Hammel I (1991) Osteopenia, hematopoiesis, and bone remodelling in iliac crest and femoral biopsies: a prospective study of 102 cases of femoral neck fractures. Bone 12:1–6
Dunstan C. Osteocyte death and hip fracture. (J Bone Min Res, this issue).
Kiel DP, Felson DT, Anderson JJ (1987) Hip fracture and the use of estrogens in postmenopausal women. N Engl J Med 317:1169–1174
Heaney RP (1990) Estrogen-calcium interactions in the postmenopause: a quantitative description. Bone Miner 11:67–84
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Parfitt, A.M. Bone age, mineral density, and fatigue damage. Calcif Tissue Int 53 (Suppl 1), S82–S86 (1993). https://doi.org/10.1007/BF01673408
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DOI: https://doi.org/10.1007/BF01673408