Alendronate and Parathyroid Hormone
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Black et al.1 and Cosman et al.2 (Aug. 11 issue) report that combinations of parathyroid hormone and alendronate are beneficial in the treatment of osteoporosis. However, it appears possible that coexisting subclinical osteomalacia may have clouded both the diagnosis and the interpretation of the results.
In a study of elderly subjects in Ireland with vitamin D deficiency, my colleagues and I observed a surprisingly larger number who had low serum levels of 25-hydroxyvitamin D as well as mildly abnormal calcium, phosphorus, and alkaline phosphatase levels.3,4 Cosman and colleagues found a similar pattern of low serum levels of 25-hydroxyvitamin D in some of their subjects, whom they treated, but the authors provided no further evidence that any possible osteomalacia was healed before the initiation of their study. Black and colleagues provide no data with regard to this question.
The apparent response to parathyroid hormone and alendronate should not be ascribed to these two agents alone, since both study protocols included simultaneous vitamin D supplementation. It remains possible that the results may have been influenced by the coincident healing of osteomalacia.
Francis P. Muldowney, M.D.
St. Vincent's University Hospital
Dublin 4, Ireland
fpmul@eircom.net
References
Black DM, Bilezikian JP, Ensrud KE, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med 2005;353:555-565.
Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R. Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med 2005;353:566-575.
McKenna M, Freaney R, Keating D, Muldowney FP. The prevalence and management of vitamin D deficiency in an acute geriatric unit. Ir Med J 1981;74:336-338.
McKenna MJ, Freaney R, Meade A, Muldowney FP. Hypovitaminosis D and elevated serum alkaline phosphatase in elderly Irish people. Am J Clin Nutr 1985;41:101-109.
Dr. Black and colleagues reply: With regard to the letter from Dr. Muldowney: we agree that vitamin D insufficiency is common among elderly persons.1 In the Parathyroid Hormone and Alendronate (PaTH) study, women with baseline serum vitamin D levels of less than 10 ng per milliliter were excluded, since that is the value below which mineralization defects have been demonstrated in histologic studies of bone.2 In addition, women with serum calcium, phosphorus, or alkaline phosphatase levels outside the normal range were excluded. Therefore, we feel that there were few participants with significant mineralization defects in this cohort.
We recognize that even with a serum vitamin D level of more than 10 ng per milliliter, increased bone turnover and elevated parathyroid hormone values can occur. However, the mean baseline serum vitamin D level was relatively high (37 ng per milliliter), and only 24 percent of subjects had values below 30 ng per milliliter. When the results were stratified according to baseline vitamin D levels (less than or more than 30 ng per milliliter), the differences among treatment groups were similar in the two subgroups. Nevertheless, we cannot say whether the results would have differed among those with much lower vitamin D levels.
An added benefit from calcium and vitamin D cannot be determined, since all treatment groups in the PaTH study (as well as those in virtually all other osteoporosis trials) received calcium and vitamin D.
Dennis M. Black, Ph.D.
Deborah Sellmeyer, M.D.
University of California, San Francisco
San Francisco, CA 94107
dblack@psg.ucsf.edu
Clifford J. Rosen, M.D.
St. Joseph Hospital
Bangor, ME 04401
References
Lips P, Duong T, Oleksik A, et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the Multiple Outcomes of Raloxifene Evaluation clinical trial. J Clin Endocrinol Metab 2001;86:1212-1221.
Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22:477-501.
Dr. Cosman and colleagues reply: We agree that vitamin D deficiency is exceptionally common among elderly people with osteoporosis. Our study design, however, precluded the inclusion of subjects with subclinical osteomalacia. To enroll in our trial, all women had to have serum 25(OH)D levels greater than 20 ng per milliliter (in some cases, after vitamin D supplementation) and normal levels of parathyroid hormone and alkaline phosphatase. Women in the two parathyroid hormone groups and those who received alendronate alone were all provided with calcium and vitamin D supplements, as needed, on the basis of dietary intake, and with weekly alendronate. Therefore, we believe that in this randomized, controlled trial, the changes in bone mineral density and biochemical changes seen in the parathyroid hormone groups were clearly due to the administration of parathyroid hormone.
Felicia Cosman, M.D.
Jeri Nieves, Ph.D.
Robert Lindsay, M.D.
Helen Hayes Hospital
West Haverstraw, NY 10993
cosmanf@helenhayeshosp.org
In a study of elderly subjects in Ireland with vitamin D deficiency, my colleagues and I observed a surprisingly larger number who had low serum levels of 25-hydroxyvitamin D as well as mildly abnormal calcium, phosphorus, and alkaline phosphatase levels.3,4 Cosman and colleagues found a similar pattern of low serum levels of 25-hydroxyvitamin D in some of their subjects, whom they treated, but the authors provided no further evidence that any possible osteomalacia was healed before the initiation of their study. Black and colleagues provide no data with regard to this question.
The apparent response to parathyroid hormone and alendronate should not be ascribed to these two agents alone, since both study protocols included simultaneous vitamin D supplementation. It remains possible that the results may have been influenced by the coincident healing of osteomalacia.
Francis P. Muldowney, M.D.
St. Vincent's University Hospital
Dublin 4, Ireland
fpmul@eircom.net
References
Black DM, Bilezikian JP, Ensrud KE, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med 2005;353:555-565.
Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R. Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med 2005;353:566-575.
McKenna M, Freaney R, Keating D, Muldowney FP. The prevalence and management of vitamin D deficiency in an acute geriatric unit. Ir Med J 1981;74:336-338.
McKenna MJ, Freaney R, Meade A, Muldowney FP. Hypovitaminosis D and elevated serum alkaline phosphatase in elderly Irish people. Am J Clin Nutr 1985;41:101-109.
Dr. Black and colleagues reply: With regard to the letter from Dr. Muldowney: we agree that vitamin D insufficiency is common among elderly persons.1 In the Parathyroid Hormone and Alendronate (PaTH) study, women with baseline serum vitamin D levels of less than 10 ng per milliliter were excluded, since that is the value below which mineralization defects have been demonstrated in histologic studies of bone.2 In addition, women with serum calcium, phosphorus, or alkaline phosphatase levels outside the normal range were excluded. Therefore, we feel that there were few participants with significant mineralization defects in this cohort.
We recognize that even with a serum vitamin D level of more than 10 ng per milliliter, increased bone turnover and elevated parathyroid hormone values can occur. However, the mean baseline serum vitamin D level was relatively high (37 ng per milliliter), and only 24 percent of subjects had values below 30 ng per milliliter. When the results were stratified according to baseline vitamin D levels (less than or more than 30 ng per milliliter), the differences among treatment groups were similar in the two subgroups. Nevertheless, we cannot say whether the results would have differed among those with much lower vitamin D levels.
An added benefit from calcium and vitamin D cannot be determined, since all treatment groups in the PaTH study (as well as those in virtually all other osteoporosis trials) received calcium and vitamin D.
Dennis M. Black, Ph.D.
Deborah Sellmeyer, M.D.
University of California, San Francisco
San Francisco, CA 94107
dblack@psg.ucsf.edu
Clifford J. Rosen, M.D.
St. Joseph Hospital
Bangor, ME 04401
References
Lips P, Duong T, Oleksik A, et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the Multiple Outcomes of Raloxifene Evaluation clinical trial. J Clin Endocrinol Metab 2001;86:1212-1221.
Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22:477-501.
Dr. Cosman and colleagues reply: We agree that vitamin D deficiency is exceptionally common among elderly people with osteoporosis. Our study design, however, precluded the inclusion of subjects with subclinical osteomalacia. To enroll in our trial, all women had to have serum 25(OH)D levels greater than 20 ng per milliliter (in some cases, after vitamin D supplementation) and normal levels of parathyroid hormone and alkaline phosphatase. Women in the two parathyroid hormone groups and those who received alendronate alone were all provided with calcium and vitamin D supplements, as needed, on the basis of dietary intake, and with weekly alendronate. Therefore, we believe that in this randomized, controlled trial, the changes in bone mineral density and biochemical changes seen in the parathyroid hormone groups were clearly due to the administration of parathyroid hormone.
Felicia Cosman, M.D.
Jeri Nieves, Ph.D.
Robert Lindsay, M.D.
Helen Hayes Hospital
West Haverstraw, NY 10993
cosmanf@helenhayeshosp.org