Based on our continued studies, we remain convinced that cyclical etidronate therapy is both safe and effective in the treatment of postmenopausal osteoporosis. Contrary to Dr. Loeliger's interpretation of our recent publication, we feel that the study results were in fact encouraging ().
Dr.Loeliger appears to have based his criticism upon vertebral fracture data derived only from year 3 to the initial study, but it is necessary to examine the entire three-year period of the study. Dr.Loeliger also suggested that the patient as the unit of observation be examined. Table 4 of our publication itemized both the incidence and rate of vertebral fracture in each study group. Regardless of the efficacy measure chosen – the rate of new vertebral fractures occurring in previously normal vertebrae, the rate of all vertebral fractures, or the percentage of patients suffering vertebral fractures over time – etidronate treatment was consistently beneficial. It is true that the favorable effect of etidronate treatment in the prevention of both new and total vertebral fractures was statistically significant at the end of 3 years only in the higher risk subpopulation, but this is a consequence of the low fracture incidence in the entire study group.
Dr.Loeliger states that the incidence of non-vertebral fractures was higher in the etidronate than in the non-etidronate groups. We took a very conservative approach to the enumeration of non-vertebral fractures, including fractures of fingers and toes and requiring only clinical confirmation of these fractures. Our accounting of fractures thus included those associated with trauma (motor vehicle accidents or assaults) or metastatic disease, as well as those that might reasonably be associated with bone fragility. When the analysis of non-vertebral fractures was limited to those most associated with aging and osteoporosis, the two groups were comparable (7 fractures per group).
Dr.Loeliger also alludes to a theoretical concern that protracted treatment with any bisphosphonate might result in a profound, undesirable decrease in bone remodelling – so-called ‘frozen bone’. It is very reassuring that there has been no clinical, biochemical, radiographic or histologic evidence for such a phenomenon, either in our United States study,2 or in extended treatment (up to 7 years) of patients in a Danish study.34
We believe that the available data from our study, coupled with the results of further treatment over a 5-year period,5 support our original conclusion: cyclical etidronate therapy appears to be safe and effective for the treatment of postmenopausal osteoporosis.
S.T. Harris
Literatuur
Harris ST, Watts NB, Jackson RD, Genant HK, Wasnich RD, Ross P, et al. Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: Three years of blinded therapy followed by one year of open therapy. Am J Med 1993;95:557-67.
Ott SM, Woodson GC, Huffer WE, Miller PD, Watts NB. Bone histomorphometric changes following cyclic therapy with phosphate and etidronate disodium in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 1994;78:968-72.
Storm T, Thamsborg G, Steiniche T, Genant HK, Sørensen OH. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990;322:1265-71.
Storm T, Steiniche T, Thamsborg G, Melsen F. Changes in bone histomorphometry after long-term treatment with intermittent cyclic etidronate for postmenopausal osteoporosis. J Bone Miner Res 1993;8:199-208.
Licata AA, Chesnut CH III, Genant HK, et al. Effects of 2 years‘ follow-up cyclical etidronate treatment in postmenopausal osteoporotic women [abstract]. J Bone Miner Res 1993;8(Suppl 1):S141.
Didrokit (etidroninezuur-calciumcarbonaat) ter behandeling van postmenopauzale osteoporose onterecht geregistreerd?
San Francisco (Calif.), July 1994,
Based on our continued studies, we remain convinced that cyclical etidronate therapy is both safe and effective in the treatment of postmenopausal osteoporosis. Contrary to Dr. Loeliger's interpretation of our recent publication, we feel that the study results were in fact encouraging ().
Dr.Loeliger appears to have based his criticism upon vertebral fracture data derived only from year 3 to the initial study, but it is necessary to examine the entire three-year period of the study. Dr.Loeliger also suggested that the patient as the unit of observation be examined. Table 4 of our publication itemized both the incidence and rate of vertebral fracture in each study group. Regardless of the efficacy measure chosen – the rate of new vertebral fractures occurring in previously normal vertebrae, the rate of all vertebral fractures, or the percentage of patients suffering vertebral fractures over time – etidronate treatment was consistently beneficial. It is true that the favorable effect of etidronate treatment in the prevention of both new and total vertebral fractures was statistically significant at the end of 3 years only in the higher risk subpopulation, but this is a consequence of the low fracture incidence in the entire study group.
Dr.Loeliger states that the incidence of non-vertebral fractures was higher in the etidronate than in the non-etidronate groups. We took a very conservative approach to the enumeration of non-vertebral fractures, including fractures of fingers and toes and requiring only clinical confirmation of these fractures. Our accounting of fractures thus included those associated with trauma (motor vehicle accidents or assaults) or metastatic disease, as well as those that might reasonably be associated with bone fragility. When the analysis of non-vertebral fractures was limited to those most associated with aging and osteoporosis, the two groups were comparable (7 fractures per group).
Dr.Loeliger also alludes to a theoretical concern that protracted treatment with any bisphosphonate might result in a profound, undesirable decrease in bone remodelling – so-called ‘frozen bone’. It is very reassuring that there has been no clinical, biochemical, radiographic or histologic evidence for such a phenomenon, either in our United States study,2 or in extended treatment (up to 7 years) of patients in a Danish study.34
We believe that the available data from our study, coupled with the results of further treatment over a 5-year period,5 support our original conclusion: cyclical etidronate therapy appears to be safe and effective for the treatment of postmenopausal osteoporosis.
Harris ST, Watts NB, Jackson RD, Genant HK, Wasnich RD, Ross P, et al. Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: Three years of blinded therapy followed by one year of open therapy. Am J Med 1993;95:557-67.
Ott SM, Woodson GC, Huffer WE, Miller PD, Watts NB. Bone histomorphometric changes following cyclic therapy with phosphate and etidronate disodium in women with postmenopausal osteoporosis. J Clin Endocrinol Metab 1994;78:968-72.
Storm T, Thamsborg G, Steiniche T, Genant HK, Sørensen OH. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990;322:1265-71.
Storm T, Steiniche T, Thamsborg G, Melsen F. Changes in bone histomorphometry after long-term treatment with intermittent cyclic etidronate for postmenopausal osteoporosis. J Bone Miner Res 1993;8:199-208.
Licata AA, Chesnut CH III, Genant HK, et al. Effects of 2 years‘ follow-up cyclical etidronate treatment in postmenopausal osteoporotic women [abstract]. J Bone Miner Res 1993;8(Suppl 1):S141.