Five years of denosumab exposure in women with postmenopausal osteoporosis: Results from the first two years of the FREEDOM extension.

in Journal of Bone and Mineral Research (2012), 27(3), 694-701

The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for treatment of postmenopausal women with osteoporosis. Participants who completed FREEDOM were eligible to ... [more ▼]

The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for treatment of postmenopausal women with osteoporosis. Participants who completed FREEDOM were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fractures rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a "virtual untreated twin" cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw (ONJ). Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk/benefit profile. (c) 2011 American Society for Bone and Mineral Research. [less ▲]

Post hoc analysis of a single IV infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis.

in Osteoporosis International (2012), 23

This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is ... [more ▼]

This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. INTRODUCTION: In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. METHODS: Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (</=3 months) subpopulations] were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. RESULTS: At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients </=74 years (P < 0.05) in the treatment and 65-74 years (P = 0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P < 0.05), cumulative prednisone dose (all P < 0.01), and postmenopausal status (all P < 0.05). In premenopausal women, in both subpopulations, zoledronic acid significantly increased total hip BMD (all P < 0.05) versus risedronate at month 12 but not LS BMD. Osteoporotic patients in the prevention (P = 0.0189) and osteopenic patients in the treatment subpopulation (P = 0.0305) showed significant LS BMD increases with zoledronic acid versus risedronate at month 12. CONCLUSIONS: This post hoc analysis suggests that zoledronic acid is significantly more effective than risedronate in increasing LS BMD in prevention and treatment of glucocorticoid-induced osteoporosis across a wide range of patients. [less ▲]

Bisphosphonates and glucocorticoid osteoporosis in men: results of a randomized controlled trial comparing zoledronic acid with risedronate.

in BONE (2012), 50

BACKGROUND: We studied 265 men (mean age 56.4years; range 18-83years), among patients enrolled in two arms of a double-blind, 1-year study comparing the effects of zoledronic acid (ZOL) with risedronate ... [more ▼]

BACKGROUND: We studied 265 men (mean age 56.4years; range 18-83years), among patients enrolled in two arms of a double-blind, 1-year study comparing the effects of zoledronic acid (ZOL) with risedronate (RIS) in patients either commencing (prednisolone 7.5mg/day or equivalent) (prevention arm, n=88) or continuing glucocorticoid therapy (treatment arm, n=177). METHODS: Patients received either a single ZOL 5mg infusion or RIS 5mg oral daily at randomization, along with calcium (1000mg) and vitamin D (400-1200IU). Primary endpoint: difference in percentage change from baseline in bone mineral density (BMD) at the lumbar spine (LS) at 12months. Secondary endpoints: percentage changes in BMD at total hip (TH) and femoral neck (FN), relative changes in bone turnover markers (beta-CTx and P1NP), and overall safety. FINDINGS: In the treatment subpopulation, ZOL increased LS BMD by 4.7% vs. 3.3% for RIS and at TH the percentage changes were 1.8% vs. 0.2%, respectively. In the prevention subpopulation, bone loss was prevented by both treatments. At LS the percentage changes were 2.5% vs. -0.2% for ZOL vs. RIS and at TH the percentage changes were 1.1% vs. -0.4%, respectively. ZOL significantly increased lumbar spine BMD more than RIS at Month 12 in both the prevention population (p=0.0024) and the treatment subpopulation (p=0.0232) in men. In the treatment subpopulation, ZOL demonstrated a significantly greater reduction in serum beta-CTx and P1NP relative to RIS at all time-points. In the prevention subpopulation, ZOL significantly reduced beta-CTx at all time-points, and P1NP at Month 3 (p=0.0297) only. Both treatments were well tolerated in men, albeit with a higher incidence of influenza-like illness and pyrexia events post-infusion with ZOL. INTERPRETATION: Once-yearly ZOL preserves or increases BMD within 1year to a greater extent than daily RIS in men receiving glucocorticoid therapy. [less ▲]

Denosumab therapy in postmenopausal women with osteoporosis : results from the first two years of the freedom trial extension

in Endocrine Reviews (2011), 32

Traitement durant cinq ans par denosumab (DMAb) chez des femmes ménopausées ostéoporotiques : résultats d'efficacité des deux premières années de l'extension de l'essai FREEDOM

in Revue du Rhumatisme (2011), 78(S5), 214

Extended safety observations from denosumab administration in postmenopausal women from FREEDOM and FREEDOM extension trials

in Arthritis and Rheumatism (2011), 63(S10), 431-432

Effectiveness of zoledronic acid in the prevention and treatment of glucocorticoid-induced osteoporosis in men and premenopausal women

in Arthritis and Rheumatism (2010, October), 62(10), 902-903

Effect of a single i.v. infusion of zoledronic acid on bone turnover markers versus oral risedronate in patients with glucocorticoid-induced osteoporosis.

in Bone (2009)

Effects of Strontium Ranelate on Spinal Osteoarthritis Progression

in Annals of the Rheumatic Diseases (2008), 67(3), 335-9

OBJECTIVE: The aim of this study was to determine whether a 3-year treatment with strontium ranelate could delay the progression of spinal osteoarthritis (OA). METHODS: This study was a post-hoc analysis ... [more ▼]

OBJECTIVE: The aim of this study was to determine whether a 3-year treatment with strontium ranelate could delay the progression of spinal osteoarthritis (OA). METHODS: This study was a post-hoc analysis of pooled data from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and TReatment Of Peripheral OSteoporosis (TROPOS) trials performed on 1105 women with osteoporosis and concomitant radiological spinal OA at baseline, and for whom lumbar x-rays were available at baseline and over the 3-year treatment period. The presence and severity of osteophytes, disc space narrowing and sclerosis in the lumbar intervertebral spaces was graded according to a validated method, and an overall OA score was calculated for each intervertebral space. Back pain (measured on a five-point Likert scale only in SOTI) and health-related quality of life (SF-36 questionnaire) were assessed at baseline and after 3 years. Patients who suffered an incident or progressive vertebral fracture during the study were excluded from the analysis. RESULTS: The proportion of patients with worsening overall spinal OA score was reduced by 42% in the strontium ranelate group, compared with placebo (RR, 0.58; 95% CI, 0.42 to 0.79; p = 0.0005). Significantly more patients in the strontium ranelate group experienced an improvement in back pain after 3 years, compared with placebo (p = 0.03), while no significant difference was observed in terms of health-related quality of life between these patient groups. CONCLUSIONS: The results of this post-hoc analysis suggest that strontium ranelate could reduce the progression of the radiographic features of spinal OA and back pain in women with osteoporosis and prevalent spinal OA. [less ▲]

Une perfusion d'acide zolédronique 5 mg est plus efficace que le risédronate 5 mg/j per os sur l'augmentation de la densité lombaire et fémorale au cours de l'ostéoporose cortisonique

in Revue du Rhumatisme (2008), 75