Osteologix, Inc (SAN FRANCISCO, California), a specialty biopharmaceutical company targeting musculoskeletal diseases, reported additional details from a phase II clinical study of NB S101 (a once-daily tablet formulation of strontium malonate), demonstrating that the osteoporosis drug candidate was well-tolerated and significantly suppressed bone resorption while simultaneously improving bone mineral density (BMD) at 12 weeks.

In the international, randomized, double-blind, active-controlled, dose-response study, 289 postmenopausal women ages >50 with low BMD were randomized to five groups. The primary endpoint was 12-week percentage change in CTX-1 (C-terminal telopeptide of type 1 collagen), a well-validated biomarker that measures bone resorption activity, with three daily doses of NB S101 (0.75 g, 1 g, or 2 g) versus placebo or the active comparator, Protelos^® (2 g, strontium ranelate, Servier). Secondary endpoints included bone formation markers and spine and hip BMD. Bone resorption assessed with the CTX-1 marker indicated a dose-dependent effect of NB S101 to reduce bone resorption. All three doses of NB S101 achieved statistically significant reductions in CTX-1, with the 2 g dose of NB S101 achieving significantly greater reductions of CTX-1 (P <.001) than the 2 g dose of Protelos. All three doses of NB S101 significantly increased BMD, as measured at the total hip and lumbar spine, in addition to being safe and well tolerated with the frequency and types of adverse events comparable to those with Protelos.

Osteologix also reported the application of inductively coupled plasma-mass spectrometry to study the incorporation of strontium into bone, bone marrow, and teeth of dogs after 1 month of treatment with strontium malonate. After 4 weeks of treatment, Bone Specific Alkaline Phosphatase (BSAP), a well validated marker of bone formation, significantly increased with a strong correlation to the bone-strontium content. In female dogs, the placebo-treated group showed a 53% decrease in BSAP, whereas the three strontium malonate-treated groups showed a 60%, 276%, and 278% increase when treated with 300, 1000, and 3000 mg/kg/day, respectively. For male dogs, the corresponding values were -44%, +142%, +194%, and +247% increases in BSAP in the placebo, 300, 1000, and 3000 mg/kg/day groups, respectively.

Protelos reduces fracture risk and is approved in Europe and other territories outside the US for the treatment of postmenopausal osteoporosis. The exact mechanism whereby strontium salts act on bone is not fully understood.