Effects of alendronate treatment on serum levels of osteoprotegerin and total receptor activator of nuclear factor kappaB in women with postmenopausal osteoporosis.
OBJECTIVE
Bisphosphonates are potent inhibitors of bone resorption that are used as effective therapeutic agents for the management of osteoporosis and other bone diseases. The osteoprotegerin (OPG)-receptor activator of nuclear factor kappaB (RANKL) system plays an important role in the regulation of bone metabolism and vascular biology. The effects of bisphosphonate treatment in OPG-RANKL system have not been fully elucidated. The aims of the study were to evaluate the effects of alendronate treatment (70 mg once/wk) on serum concentrations of OPG, total RANKL, and biochemical markers of bone turnover in untreated women with postmenopausal osteoporosis and to determine the correlation between changes in bone mineral density and changes in serum OPG, total RANKL, and bone turnover markers.


METHODS
The study was a single group pretest/posttest design including a total number of 46 participants. Serum OPG and total RANKL serum levels were determined before and after 3, 6, and 12 months of treatment with alendronate. We also measured serum carboxyterminal cross-linked telopeptide of type I collagen, osteocalcin, and bone-specific alkaline phosphatase. The main outcome measures are the changes in OPG and total RANKL serum levels after alendronate treatment.


RESULTS
Serum OPG changes were not significant at 3 and 6 months (-1.6% and -1%), but at 12 months, there was a significant reduction of 6.5% (P < 0.01). Total RANKL serum levels increased during treatment: 23% at 3 months, 25% at 6 months, and 52% at 12 months (P < 0.001 for all comparisons). Basal levels of OPG, total RANKL, and bone turnover markers were not correlated, and we did not find correlations between changes in these parameters after treatment.


CONCLUSIONS
We conclude that the determination of total RANKL integrates the free RANKL and the fraction bound to OPG. The apparent decrease in the serum levels of OPG might reflect an increase in OPG binding to RANKL, which results in a beneficial effect on bone.
Reyes-García
Rebeca
R
Bone Metabolic Unit, Endocrinology Division, San Cecilio University Hospital, Granada, Spain. rebecarg@yahoo.com
Muñoz-Torres
Manuel
M
García
D Fernández
DF
Mezquita-Raya
Pedro
P
García Salcedo
Jose Antonio
JA
de Dios Luna
Juan
J
D000368:Aged; D019386:Alendronate / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy*; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*
D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D019386:Alendronate