Prevention of glucocorticoid induced osteoporosis with alendronate or alfacalcidol: relations of change in bone mineral density, bone markers, and calcium homeostasis.
OBJECTIVE
To explore the relation of changes in measures of bone turnover and changes in bone mineral density (BMD) of the lumbar spine and total hip over 18 months in a double-blinded, randomized trial, comparing the effect of alfacalcidol (101 patients) versus alendronate (100 patients) on BMD in patients who recently started treatment with glucocorticoids for various rheumatic diseases.


METHODS
Associations between changes in serum procollagen type I C-propeptide (P1CP), fasting urine N-terminal telopeptide of type I collagen (NTx), serum calcium, parathyroid hormone (PTH), osteocalcin, and change from baseline in BMD over 18 months were explored with regression and correlation analyses.


RESULTS
In both treatment groups, there was a statistically significant decrease in NTx. In the alfacalcidol group there was also a significant increase in P1CP and osteocalcin, in contrast to the alendronate group, but BMD in the alfacalcidol decreased versus an increase in the alendronate group (p < 0.001). In neither treatment group were changes in biochemical measures correlated with the change in BMD, with the exception of a negative correlation in the alendronate group between changes in total hip BMD and NTx. Use of alendronate resulted in an increased PTH in 27 patients, but the increase in BMD of these patients was not statistically significantly different compared to patients taking alendronate with normal PTH levels.


CONCLUSIONS
Changes in BMD were not associated with changes in bone measures, with the exception of NTx in the alendronate group. For the patient taking glucocorticoids in clinical practice, the value of serial assessment of bone markers is low; changes in markers are no substitute for changes in BMD. ClinicalTrials.gov number: NCT00138983.
Jacobs
Johannes W G
JW
Department of Rheumatology and Clinical Immunology and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. J.W.G.Jacobs@UMCUtrecht.nl
de Nijs
Ron N J
RN
Lems
Willem F
WF
Geusens
Piet P M M
PP
Laan
Roland F J
RF
Huisman
Anne-Margriet
AM
Algra
Ale
A
Buskens
Erik
E
Hofbauer
Lorenz C
LC
Oostveen
Ans C M
AC
Bruyn
George A W
GA
Dijkmans
Ben A C
BA
Bijlsma
Johannes W J
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D024042:Collagen Type I / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010281:Parathyroid Hormone / Q000097:blood; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000652:urine; D011347:Procollagen / Q000378:metabolism
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D005938:Glucocorticoids; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D002118:Calcium; C008088:alfacalcidol; D019386:Alendronate