Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women.

The mean degree of mineralization of bone (MDMB) was measured by quantitative microradiography on transiliac bone biopsies taken from 53 postmenopausal osteoporotic women who had been treated with alendronate (ALN; 10 mg/day) during 2 (9 patients) or 3 years (16 patients) or with placebo (PLA; 15 and 13 patients, respectively). In the same patients, bone mineral density (BMD) values were obtained by dual-energy X-ray absorptiometry of the lumbar spine and femoral neck at the beginning and end of treatment. Histomorphometric parameters and activation frequency of new remodeling units were also measured on the iliac biopsies. After 2 years of ALN, MDMB in compact bone was 9.3% (p = 0.0035) and in cancellous bone was 7.3% (p = 0.0009) higher, respectively, than PLA. After 3 years of ALN, MDMB in compact bone was 11.6% (p = 0.0002) and in cancellous bone was 11.4% (p = 0.0001) higher, respectively, than PLA. After 2 and 3 years of ALN, and compared with the corresponding PLA, the distribution of the degree of mineralization in compact and cancellous bone showed a clear shift toward the highest mineralization values and a decrease in the number of bone structure units having low values of mineralization. The between-group differences in MDMB were similar to those of BMD at the lumbar spine BMD (+8.7% after 2 years and +9.6% after 3 years, respectively), suggesting that MDMB augmentation probably accounted for the majority of the increase in BMD seen with ALN. The data support the hypothesis that the reduction in activation frequency caused by the antiresorptive effect of ALN is followed by a prolonged secondary mineralization that increases the percentage of bone structure units having reached a maximum degree of secondary mineralization and, through this mechanism, MDMB. That these effects contribute to improved bone strength is demonstrated by the reduction in fracture incidence previously demonstrated in these patients.

[1]  E. Barrett-Connor,et al.  Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial. , 1997, Archives of internal medicine.

[2]  H. Fleisch.  Bisphosphonates in Bone Disease: From the Laboratory to the Patient , 2000 .

[3]  S. Cummings,et al.  Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures , 1996, The Lancet.

[4]  G. Dickson.  Methods of Calcified Tissue Preparation , 1984 .

[5]  C. Baud,et al.  Morphological and Crystallographic Analysis of Bone Mineral , 1975 .

[6]  Jenifer Jowsey.  The Bone Biopsy , 1977 .

[7]  H. Fleisch.  Bisphosphonates: Mechanisms of Action , 1998 .

[8]  P. Fratzl,et al.  Validation of quantitative backscattered electron imaging for the measurement of mineral density distribution in human bone biopsies. , 1998, Bone.

[9]  P. Delmas,et al.  Prevention of early postmenopausal bone loss with cyclical etidronate therapy (a double-blind, placebo-controlled study and 1-year follow-up) , 1997, The Journal of clinical endocrinology and metabolism.

[10]  J Dequeker,et al.  Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. , 1995, The New England journal of medicine.

[11]  D. Felsenberg,et al.  Multinational, Placebo-Controlled, Randomized Trial of the Effects of Alendronate on Bone Density and Fracture Risk in Postmenopausal Women with Low Bone Mass: Results of the FOSIT Study , 1999, Osteoporosis International.

[12]  G. Rodan,et al.  Mechanisms of action of bisphosphonates. , 1998, Annual review of pharmacology and toxicology.

[13]  A. Boskey,et al.  FTIR Microspectroscopic Analysis of Normal Human Cortical and Trabecular Bone , 1997, Calcified Tissue International.

[14]  D. Kimmel,et al.  Dose-Response Relationships for Alendronate Treatment in Osteoporotic Elderly Women , 1997 .

[15]  G Boivin,et al.  Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. , 1997, Bone.

[16]  A. Boyde,et al.  Changes in the mineral density distribution in human bone with age: Image analysis using backscattered electrons in the SEM , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  J. Jowsey.  Metabolic diseases of bone , 1977 .

[18]  J. Tucci,et al.  Effect of three years of oral alendronate treatment in postmenopausal women with osteoporosis. , 1996, The American journal of medicine.

[19]  S. Krane,et al.  Metabolic bone disease , 1977 .

[20]  A. LaCroix,et al.  Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. , 1998, JAMA.

[21]  P. Fratzl,et al.  Mineralization of cancellous bone after alendronate and sodium fluoride treatment: a quantitative backscattered electron imaging study on minipig ribs. , 1997, Bone.

[22]  P. Fratzl,et al.  Effects of sodium fluoride and alendronate on the bone mineral in minipigs: A small‐angle X‐ray scattering and backscattered electron imaging study , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[23]  H. Kruse,et al.  Calcium Metabolism, Bone and Metabolic Bone Diseases , 1975, Springer Berlin Heidelberg.

[24]  John A. Kanis,et al.  Bone and Mineral Research , 1991 .

[25]  R. Francis.  Bisphosphonates in the treatment of osteoporosis in 1997: a review , 1997 .

[26]  Lynn Wei,et al.  Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. , 1997, The Journal of clinical investigation.

[27]  P. Meunier,et al.  Histomorphometric Methods Applied to Bone , 1993 .

[28]  C Marcelli,et al.  Markers of bone resorption predict hip fracture in elderly women: The EPIDOS prospective study , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  E. Opas,et al.  The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates. , 1993, The Journal of clinical investigation.

[30]  A. Boskey,et al.  FTIR Microspectroscopic Analysis of Human Iliac Crest Biopsies from Untreated Osteoporotic Bone , 1997, Calcified Tissue International.

[31]  G. Rodan,et al.  Bone mass homeostasis and bisphosphonate action. , 1997, Bone.