4.5 Article

Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis

Journal

OSTEOPOROSIS INTERNATIONAL
Volume 21, Issue 12, Pages 2027-2036

Publisher

SPRINGER LONDON LTD
DOI: 10.1007/s00198-009-1168-7

Keywords

Alendronate; Biochemical markers; Bone turnover; Histomorphometry; Osteoporosis; Teriparatide

Funding

  1. Eli Lilly and Company [NCT00191893]
  2. Alliance for Better Bone Health
  3. Amgen

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The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1-34), TPTD) is similar in patients who were either treatment-nave (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy. Introduction Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment. Methods Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5+/-16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end. Results Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11-0.34 cycles per year, 3.96-9.8% in the ALN-pretreated group and 0.19-0.33 cycles per year, 6.2-11.3% (p<0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum aminoterminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r=0.57, p<0.001 and r=0.48, p<0.01) and OS (r=0.51, p<0.01 and r=0.56, p<0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r=0.52, p<0.01) and OS (r=0.54, p<0.01) after 24 months. Conclusions The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.

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