title: Effects of alendronate on bone quality and remodeling in glucocorticoid-induced osteoporosis: a histomorphometric analysis of transiliac biopsies.
abstract: Effects of alendronate (ALN) on bone quality and turnover were assessed in 88 patients (52 women and 36 men aged 22-75 years) who received long-term oral glucocorticoid exposure. Patients were randomized to receive oral placebo or alendronate 2.5, 5, or 10 mg/day for 1 year and stratified according to the duration of their prior glucocorticoid treatment. Transiliac bone biopsies were obtained for qualitative and quantitative analysis after tetracycline double-labeling at the end of 1 year of treatment. As previously reported in glucocorticoid-induced osteoporosis, low cancellous bone volume and wall thickness were noted in the placebo group as compared with normal values. Alendronate treatment was not associated with any qualitative abnormalities. Quantitative comparisons among the four treatment groups were performed after adjustment for age, gender, and steroid exposure. Alendronate did not impair mineralization at any dose as assessed by mineralization rate. Osteoid thickness (O.Th) and volume (OV/BV) were significantly lower in alendronate-treated patients, irrespective of the dose (P = 0.0003 and 0.01, respectively, for O.Th and OV/BV); however, mineral apposition rate was not altered. As anticipated, significant decreases of mineralizing surfaces (76% pooled alendronate group; P = 0.006), activation frequency (-72%; P = 0.004), and bone formation rate (-71%; P = 0.005) were also noted with alendronate treatment. No significant difference was noted between the changes observed with each dose. Absence of tetracycline label in trabecular bone was noted in approximately 4% of biopsies in placebo and alendronate-treated groups. Trabecular bone volume, parameters of microarchitecture, and resorption did not differ significantly between groups. In conclusion, alendronate treatment in patients on glucocorticoids decreased the rate of bone turnover, but did not completely suppress bone remodeling and maintained normal mineralization at all alendronate doses studied. Alendronate treatment did not influence the osteoblastic activity, which is already low in glucocorticoid-induced osteoporosis.
authors.affiliation: INSERM Unité 403, Faculté de Médecine RTH Laënnec, Lyon, France.
authors.forename: P M
authors.initials: PM
authors.lastname: Chavassieux
authors.forename: M E
authors.initials: ME
authors.lastname: Arlot
authors.forename: J P
authors.initials: JP
authors.lastname: Roux
authors.forename: N
authors.initials: N
authors.lastname: Portero
authors.forename: A
authors.initials: A
authors.lastname: Daifotis
authors.forename: A J
authors.initials: AJ
authors.lastname: Yates
authors.forename: N A
authors.initials: NA
authors.lastname: Hamdy
authors.forename: M P
authors.initials: MP
authors.lastname: Malice
authors.forename: D
authors.initials: D
authors.lastname: Freedholm
authors.forename: P J
authors.initials: PJ
authors.lastname: Meunier
mesh_terms: D000328:Adult; D000368:Aged; D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D002113:Calcification, Physiologic; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007085:Ilium / Q000473:pathology / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology
chemical_list: D005938:Glucocorticoids; D019386:Alendronate