PURPOSE: Concerns exist that inhaled corticosteroids may increase risk for bone disorders in patients with COPD. Effects of BUD/FM pMDI on BMD were examined.
METHODS: In this 12-month randomized, double-blind, parallel-group, multicenter trial (NCT00206167 [N=1964]; Drugs. 2009;69:549-65), BMD was assessed at baseline and 12 months in a subset (n=326 with baseline and postbaseline BMD measurements) of patients ≥40 years with moderate to very severe COPD receiving twice-daily BUD/FM pMDI 320/9μg, BUD/FM pMDI 160/9μg, FM dry powder inhaler (DPI) 9μg, or placebo. Dual-energy x-ray absorptiometry (DEXA) scans were performed. Mean changes from baseline to end of treatment (EOT) in total lumbar spine (L2, L3, L4 vertebrae) and total hip (femoral neck, trochanter, intertrochanter regions) BMD (g/cm²) were compared between treatments using analysis of covariance. BMD was further evaluated based on T-scores, in which individual BMD scores were compared with peak adult bone mass of young, healthy individuals, specific to gender.
RESULTS: Across treatments, BMD was stable over the 12-month treatment period, with only minimal shifting toward lower BMD scores from baseline to EOT. BMD mean changes from baseline to EOT were close to 0 (range: -0.01 to 0.01) in all treatment groups for spine (n=320) and hip (n=318). Geometric least squares mean ratios for all pairwise treatment group comparisons were close to 1.0 (0.98 to 1.01); all 95% CIs included 1.0. No patient with normal baseline BMD (T-score ≥-1.0 [spine, n=138; hip, n=152]) shifted to osteoporosis [T-score ≤-2.5]) at EOT. Numbers of patients exhibiting shifts from normal to osteopenia (T-score >-2.5 to <-1.0) (spine, n=14; hip, n=11) or osteopenia to osteoporosis (spine, n=9; hip, n=3) were small and distributed similarly across treatments.
CONCLUSION: Findings suggest no evidence of a clinically meaningful effect of BUD/FM pMDI on BMD assessments over the 12-month treatment period.
CLINICAL IMPLICATIONS: Results contribute important information surrounding the effect of BUD/FM pMDI on bone disorders in patients with moderate to very severe COPD, although longer-term studies may be needed for a thorough evaluation of such effects.
DISCLOSURE: Stephen Rennard, Grant monies (from industry related sources) This study was funded by AstraZeneca LP. Stephen I Rennard has received grant monies from Almirall, AstraZeneca, Biomark, Centocor, GSK, IFSH, Lorillard, Novartis, Pfizer, Philip Morris, Roche.; Shareholder Ubaldo J. Martin is a shareholder of AstraZeneca stocks.; Employee Lisa J. Suchower and Ubaldo J. Martin are employees of AstraZeneca.; Consultant fee, speaker bureau, advisory committee, etc. Stephen I Rennard is a consultant to Abbott, Able Associates, Almirall, Almirall/Forest, Altana, Anthera, APT Pharma/Britnall, Aradigm, AstraZeneca, Boehringer Ingelheim, Britnall and Nicolini, Defined Health, Dunn Group, Eaton Associates, Gerson, GSK, Infomed, Johnson & Johnson, KOL Connection, Leerink Swan, MedaCorp, Mpex, Novartis, Otsuka, Pfizer, Propagate, Pulmatrix, Quintiles, Roche, Scimed, TargeGen, Theravance, United Biosource, Vantage Point, VantagePoint Mgmt; and on the Advisory Board of Abbott, Almirall, Boehringer Ingelheim, COPDForum, Dey, GSK, Novartis, Nycomed, Nycomed/Strategicare, Pfizer, Pharmaxis, Schering-Plough, TargeGen.; Other Stephen I Rennard is a speaker for ACCP, AstraZeneca, Novartis, Network for Continuing Ed, Pfizer, SOMA, Creative Educational Concept, France Foundation. Donald P Tashkin has received grant support (administered through his university), fees for consulting/advisory boards, and/or honoraria for speaking from Boehringer Ingelheim, Pfizer, AstraZeneca, GSK, Schering-Plough, Novartis, Teva, and Dey Labs.; No Product/Research Disclosure Information