ABSTRACT
OBJECTIVES: To assess the effects of intramuscular (im) neridronate (NE) on lumbar and femoral neck BMD and on markers of bone turnover in rheumatic patients under chronic low-dose glucocorticoids (GC) therapy. METHODS: Sixty-nine osteopoenic and osteoporotic patients, affected by rheumatic diseases and gastric or esophageal conditions which contraindicated treatment with oral bisphosphonates (BPs), were randomly assigned to: Group A (23 patients) administered with daily calcium 1 g and vitamin D 800 UI; Group B (46 patients) receiving daily calcium 1 g, vitamin D 800 UI and im NE 25 mg monthly. RESULTS: After 12 months of therapy (M12) lumbar BMD was reduced of 2.97% in Group A, and improved of 3.34% (p=0.001) in Group B; at M12, femoral neck BMD was reduced of 2.40% in Group A and improved of 1.78% in Group B (p=0.010). After 6 (M6) and 12 months of therapy, the bone resorption markers were significantly reduced in Group B: OHPr-41.64% at M6 (p<0.001) and -37.91% at M12 (p<0.001); DPD-33.4% at M6 (p<0.001) and -33.18% (p<0.001) at M12: NTX -57.08% (p<0.001) at M6 and -55.95% (p<0.001) at M12; OC-11.62% (p=0.05) at M6 and -12.62% at M12 (p=0.06); B-ALP -13.95 % at M6 (p=0.04) and -0.85% at M12 (NS). CONCLUSION: A twelve-month intramuscular NE treatment in rheumatic patients under GCs therapy improves lumbar and femoral BMD and mainly reduces the markers of bone resorption.
Subject(s)
Antirheumatic Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Bone Resorption/drug therapy , Diphosphonates/therapeutic use , Glucocorticoids/adverse effects , Rheumatic Diseases/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Bone Density/drug effects , Bone Density/physiology , Bone Density Conservation Agents/administration & dosage , Bone Resorption/blood , Bone Resorption/physiopathology , Diphosphonates/administration & dosage , Drug Therapy, Combination , Female , Femur/drug effects , Femur/metabolism , Humans , Injections, Intramuscular , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/metabolism , Male , Middle Aged , Osteoporosis/chemically induced , Osteoporosis/drug therapy , Osteoporosis/metabolism , Rheumatic Diseases/blood , Rheumatic Diseases/complications , Young AdultABSTRACT
Osteoprotegerin (OPG) serves as a soluble decoy receptor for RANKL to inhibit osteoclast formation and activity. Hormones such as PTH and glucocorticoids have been reported to decrease OPG concentrations, while estrogens, transforming growth factor b, related bone morphogenic factor and thrombopoietin reportedly enhance the OPG production in the osteoblastic and bone stromal cells. Since bone turnover shows a prominent circadian rhythm in laboratory animals and humans, with bone resorption increasing at night, we investigated the time structure of circulating OPG concentrations in a group of nine healthy subjects (six women and three men; in the age range of 26-49 years). Blood samples for OPG determination were collected every 4 h for 24 h on the same day, starting at 08:00 in the morning. Data were analyzed by inferential statistical procedures, including the single and population-mean cosinor. A 12-h component was found to characterize serum OPG concentrations (P = 0.038) with peak concentrations around noon and midnight. No statistically significant circadian rhythm of OPG concentrations could be found by cosinor in our study population. The mean 24-h OPG concentration was higher in women than in men (mean +/- S.E.: 3.13 +/- 0.44 vs. 1.94 +/- 0.26 pmol/l, Student t = 2.325, P = 0.053). Since PTH concentrations also exhibit a bimodal pattern along the 24-h scale, PTH may be tested as a putative determinant of the observed changes in serum concentrations of osteoprotegerin.