To the Editor:

At the 1993 Osteoporosis Conference in Hong Kong, Larry Riggs and myself each proposed that high bone turnover made an independent contribution to vertebral fracture risk that was not captured by bone densitometry. Riggs et al.'s proposal(1) was based on a reanalysis of a controlled trial of dermal estrogen,(2) mine(3) was on a more theoretical analysis of qualitative contributions to bone fragility. We were struck by the similarity of our conclusions reached from different starting points, but our plans to write a joint paper were frustrated by the pressure of other commitments and the infrequency of our meetings. Subsequently, Riggs et al. published a more detailed version of his analysis in a symposium,(4) and I developed my ideas in a book chapter.(5)

In their recent editorial, Riggs and Melton(6) revisit their earlier paper(4) and review more recent data supporting the same conclusion—that high bone turnover is intrinsically harmful. I remain in complete agreement with this conclusion, but it is necessary to define more clearly the circumstances in which it applies. Also, I believe that the mechanism I proposed in 1993 is more plausible, more subtle, and more versatile than the perforative resorption described by Drs. Riggs and Melton.

For high turnover to constitute what I refer to as a mechanical threat, some horizontally oriented trabeculae must have been removed by the mechanism that our group suggested in 1983,(7) and that was later confirmed by Eriksen et al.(8) and endorsed by Riggs and Melton,(6) which withdraws lateral support from the remaining vertically oriented trabeculae that bear the compressive loads. The resistance to buckling decreases as the square of the increase in unsupported length.(9) A contributory factor is that residual vertical trabeculae slowly become thinner with increasing age.7

Each episode of bone remodeling that occurs on a thin unsupported vertical trabecula, as found in most women more than 5 years postmenopause,(10) acts as a stress concentrator,(11) and represents a focal weakness that poses a small risk of buckling, because even a normal-sized resorption cavity may penetrate halfway or more through a trabecula.(3) For this effect, it is not necessary for the resorptive process to perforate the trabecula; being present is enough. Consequently, when turnover increases, the risk of buckling will increase within only a few weeks, as the number of resorption sites increases—it is not necessary for additional irreversible bone destruction to occur. Conversely, when turnover falls, the risk of buckling falls within a few weeks, long before there has been any measurable increase in bone mass. Such a modification of the mechanism supports Drs. Riggs and Melton's suggestion that only a small effective dose of an antiresorptive agent may be sufficient to abrogate the mechanical threat.


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  • 1
    Riggs BL, Melton LJ III, O'Fallon WM 1993 Toward optimal therapy of established osteoporosis: Evidence that antiresorptive and formation-stimulating regimens decrease vertebral fracture rate by independent mechanisms. In: Christiansen C, Riis B (eds.) Proceedings of the Fourth International Symposium on Osteoporosis, Hong Kong. Handelstrykkeriet Aalborg ApS, Aalborg, Denmark, pp. 1315.
  • 2
    Lufkin EG, Wahner HW, O'Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, Judd HL, Caplan RH, Riggs BL 1992 Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 117:19.
  • 3
    Parfitt AM 1993 Pathophysiology of bone fragility. In: Christiansen C, Riis B (eds.) Proceedings of the Fourth International Symposium on Osteoporosis, Hong Kong. Handelstrykkeriet Aalborg ApS, Aalborg, Denmark, pp. 164166.
  • 4
    Riggs BL, Melton LJ III, O'Fallon WM 1996 Drug therapy for vertebral fractures in osteoporosis: Evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficiency. Bone 18(Suppl):197S201S.
  • 5
    Parfitt AM 1996 Skeletal heterogeneity and the purposes of bone remodeling: Implications for the understanding of osteoporosis. In: MarcusR, FeldmanD, KelseyJ (eds.) Osteoporosis. Academic Press, San Diego, CA, USA, pp. 315329.
  • 6
    Riggs BL, Melton LJ III 2002 Bone turnover matters: The raloxifene treatment paradox of dramatic decreases in vertebral fractures without commensurate increases in bone density. J Bone Miner Res 17:1114.
  • 7
    Parfitt AM, Mathews CHE, Villanueva AR, Kleerekoper M, Frame B, Rao DS 1983 Relationship between surface, volume and thickness of iliac trabecular bone in aging and in osteoporosis: Implications for the microanatomic and cellular mechanism of bone loss. J Clin Invest 72:13961409.
  • 8
    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 14:12171221.
  • 9
    Kleerekoper M, Dickie D, Feldkamp LA, Goldstein SA, Flynn MJ, Parfitt AM 1987 Cancellous bone architecture and bone strength. In: ChristiansenC, JohansenC, RiisBJ (eds.) Osteoporosis. Copenhagen, Osteopress ApS, pp. 294300.
  • 10
    Mosekilde L 1988 Age-related changes in vertebral trabecular bone architecture—assessed by a new method. Bone 9:247250.
  • 11
    Einhorn TA 1992 Bone strength: The bottom line. Calc Tis Int 51:333339.