Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial.

in Annals of the Rheumatic Diseases (2013), 72(2), 179-86

BACKGROUND: Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its ... [more ▼]

BACKGROUND: Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis. METHODS: Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5-5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). RESULTS: The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56) mm; 2 g/day: -0.27 (SD 0.63) mm; placebo: -0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p=0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. CONCLUSIONS: Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day. [less ▲]

Severity of incident vertebral fracture and future fracture risk: a 3-year prospective study

in Annals of the Rheumatic Diseases (2012, June), 71(Suppl.3), 716

Radiological and clinical profil of osteoarthritic patients undergoing of total joint replacement

in Annals of the Rheumatic Diseases (2012, June), 71(Suppl.3), 693

A very high prevalence of vitamin D inadequacy combined with low dietary calcium intake is found in European postmenopausal women

in Annals of the Rheumatic Diseases (2012, June), 71(Suppl.3), 716

Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis : a randomized, double-blind, placebo-controlled international trial

in Annals of the Rheumatic Diseases (2012), 71(3), 693

Treatment of postmenopausal women with osteoporosis for six years with denosumab : three-year results from the freedom extension

in Annals of the Rheumatic Diseases (2012), 71(3), 588

Biomarkers and personalised medicine in rheumatoid arthritis: a proposal for interactions between academia, industry and regulatory bodies.

in Annals of the Rheumatic Diseases (2011), 70(10), 1713-8

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such ... [more ▼]

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such heterogeneity is also reflected in the large number of treatment targets and options. A growing number of biologics as well as small molecules are already in use and there are promising new drugs in development. In order to make the best use of treatment options, both targeted and non-targeted biomarkers have to be identified and validated. To this aim, new rules are needed for the interaction between academia and industry under regulatory control. Setting up multi-centre biosample collections with clear definition of access, organising early, possibly non-committing discussions with regulatory authorities, and defining a clear route for the validation, qualification and registration of the biomarker-drug combination are some of the more critical areas where effective collaboration between the drug industry, academia and regulators is needed. [less ▲]

Treatment of postmenopausal women with osteoporosis for 5 years with denosumab : two-year results from the FREEDOM trial extension

in Annals of the Rheumatic Diseases (2011), 70(S3), 166-167

Fibulin-3 fragments (FIB3-1 and FIB3-2) are potential new biomarkers for the diagnosis of osteoarthritis

in Annals of the Rheumatic Diseases (2011), 70(Suppl 3), 354

Mitochondrial DNA haplogroups and serum levels of proteolytic enzymes in patients with osteoarthritis.

in Annals of the Rheumatic Diseases (2011), 70(4), 646-52

OBJECTIVE: To analyse the influence of mitochondrial DNA haplogroups, as well as the radiographic grade, on serum levels of proteolytic enzymes in patients with osteoarthritis (OA). METHODS: Serum levels ... [more ▼]

OBJECTIVE: To analyse the influence of mitochondrial DNA haplogroups, as well as the radiographic grade, on serum levels of proteolytic enzymes in patients with osteoarthritis (OA). METHODS: Serum levels of metalloproteinase-1 (MMP-1), MMP-3, MMP-13, myeloperoxidase and cathepsin K were analysed in 73 patients with OA and 77 healthy controls carrying the haplogroups J, U and H, by ELISA. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L) scoring from grade 0 to grade IV. Non-parametric and multiple regression analyses were performed to test the effects of clinical variables, including gender, age, smoking status, diagnosis, haplogroups and radiological K/L grade on serum levels of these enzymes. RESULTS: A significant influence of the haplogroups on the serum levels of MMP-3 and MMP-13 was detected (p=0.027 and p=0.035, respectively). Patients with OA with haplogroup H showed higher serum levels of MMP-3 than healthy controls. Serum levels of MMP-13 were significantly higher in patients with OA (p<0.001), and carriers of the haplogroup J showed lower levels than H carriers. Besides, levels of MMP-13 were proportionally higher in radiological groups B (K/L grade II and III) and C (K/L grade IV) than in group A (K/L grade 0 and I) (p=0.005). CONCLUSIONS: This study shows that haplogroups have a significant influence on serum levels of MMP-3 and MMP-13. The influence of the haplogroups on serum levels of MMP-3 is clearly dependent on the diagnosis, whereas the influence of the haplogroups on serum levels of MMP-13 is independent of diagnosis. [less ▲]