Electronic Letters to:

Endocrine Care: Paul D. Miller, Pierre D. Delmas, Robert Lindsay, Nelson B. Watts, Marjorie Luckey, Jonathan Adachi, Kenneth Saag, Susan L. Greenspan, Ego Seeman, Steven Boonen, Suzanne Meeves, Thomas F. Lang, John P. Bilezikian for the Open-label Study to Determine How Prior Therapy with Alendronate or Risedronate in Postmenopausal Women with Osteoporosis Influences the Clinical Effectiveness of Teriparatide Investigators Early Responsiveness of Women with Osteoporosis to Teriparatide After Therapy with Alendronate or Risedronate J Clin Endocrinol Metab 2008; 93: 3785-3793 [Abstract] [Full text] [PDF]

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Response to Teriparatide after Therapy with Alendronate or Risedronate

Fernando Marin, Eugene V. McCloskey1, Steven Boonen2, Thomas N. Nickelsen3, Barbara Obermayer-Pietsch4, Fernando Marin3. 1University of Sheffield, Sheffield, UK; 2Leuven University, Leuven, Belgium; 3Lilly Research Center, UK; 4Graz University, Graz, Austria.   (4 November 2008)

Response to Teriparatide after Therapy with Alendronate or Risedronate 4 November 2008
Fernando Marin, Endocrine Medical research, LRC Department of Medical Research, Lilly Research Center, Windlesham,United Kingdom, Eugene V. McCloskey1, Steven Boonen2, Thomas N. Nickelsen3, Barbara Obermayer-Pietsch4, Fernando Marin3. 1University of Sheffield, Sheffield, UK; 2Leuven University, Leuven, Belgium; 3Lilly Research Center, UK; 4Graz University, Graz, Austria. Send letter to journal: Re: Response to Teriparatide after Therapy with Alendronate or Risedronate marin_fernando{at}lilly.com Fernando Marin, et al.	We read with interest the report by Miller et al. on the response to 12 months of teriparatide treatment in osteoporotic women who were previously treated with alendronate or risedronate in the OPTAMISE study (1). The authors showed slightly earlier increases in the biochemical markers of bone turnover during the early phase of teriparatide treatment in the prior risedronate group, as well as greater 12-month increases in areal and volumetric bone mineral density (BMD) compared with the prior alendronate group. The authors did not quote the results of a subgroup analysis of the EUROFORS trial, which included 107 and 59 postmenopausal women who were previously treated with alendronate or risedronate, respectively (2). We showed similar results to the OPTAMISE study in the bone formation markers, with statistically significant greater increases after 1 and 6 months of teriparatide treatment in P1NP and bone specific alkaline phosphatase in the prior risedronate group of doubtful clinical significance. Lumbar spine and hip BMD were not statistically significant at 6, 12, 18, or 24 months of teriparatide treatment between the two groups (2). Our analysis concurs with OPTAMISE in that the duration of prior bisphosphonate therapy did not appear to contribute to differences in responsiveness to teriparatide. Miller et al. quoted the EUROFORS quantitative computed tomography substudy (3) to suggest that different responses to teriparatide can occur as a function of prior antiresorptive therapy (1), when the findings and conclusion of that paper were just the opposite: the increase in volumetric lumbar spine BMD measured with a conventional software (QCT-Pro) or with a high-resolution scan protocol was not affected by prior antiresorptive treatment. Finally, we would like to comment on the differences in the frequency of hypercalcemia described in OPTAMISE and the EUROFORS subgroup analysis (2). In EUROFORS, teriparatide pre-dose hypercalcemia was reported in 6.5% and 8.5% of alendronate and risedronate pre-treated patients, respectively. It is not clear in the OPTAMISE report whether the incidence of 14.6% and 13.9% in prior risedronate and alendronate users refers to developing “increased” calcium levels (increase >0.3 mmol/l) or true hypercalcemia. In any case, serum calcium was measured after the patient’s morning administration of teriparatide, when the greatest effect on serum calcium is expected. References 1. Miller PD, Delmas PD, Lindsay R, Watts NB, Luckey M, Adachi J, Saag K, Greenspan SL, Seeman E, Boonen S, Meeves S, Lang TF, Bilezikian JP. 2008 Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate. J Clin Endocrinol Metab 93:3785-3793 2. Boonen S, Marin F, Obermayer-Pietsch B, Simões ME, Barker C, Glass EV, Lyritis G, Oertel H, Nickelsen T, McCloskey EV for the Eurofors Investigators. 2008 Effects of prior antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 93:852-860 3. Graeff C, Timm W, Nickelsen TN, Farrerons J, Marin F, Barker C, Glüer C-C for the EUROFORS High Resolution Quantitative Computed Tomography Substudy Group. 2007 Monitoring teriparatide associated changes in vertebral microstructure by high-resolution computed tomography in vivo: results from the EUROFORS study. J Bone Miner Res 22:1426-1433