Impact of a dietary intervention with French maritime pine bark extract (Pycnogenol®) on bone turnover markers in women with osteoporotic bone loss: a randomized, placebo-controlled double-blind study—Part I

Introduction Osteoporosis is a highly prevalent health concern both in terms of disability to an individual and costs to society. While antiresorptive drugs are the standard treatment, nutritional supplementation may offer additional advantages, particularly in the pre-therapeutic stage of osteopenia or clinically stable osteoporosis. The French maritime pine bark extract Pycnogenol ® exhibits antioxidant and anti-inflammatory properties, but its influence on bone turnover has not been investigated in humans yet. Methods In this randomized, placebo-controlled, double-blind clinical trial, 67 women received either Pycnogenol ® (100 mg twice daily; n = 33) or placebo ( n = 34) during a 3-month placebo-controlled phase, followed by a 3-month active-treatment extension, in which all participants took Pycnogenol ® . The primary endpoint included changes in the bone resorption marker C-terminal telopeptide of type I collagen (CTX-1) and bone formation marker procollagen type I N propeptide (P1NP) in serum. Secondary endpoints comprised other bone turnover markers (N-terminal telopeptide of type I collagen, NTX-1; tartrate-resistant acid phosphatase 5b, TRAP5b; bone sialoprotein, BSP), an inflammatory marker (interleukin-6, IL-6), the microbial metabolite 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (M1), and in vitro differentiation experiments with human mesenchymal stromal cells (hMSCs). Results Within the Pycnogenol ® group, serum CTX-1 levels were significantly reduced after both three ( p = 0.0327) and 6 months ( p = 0.0227) compared to baseline, while no between-group differences were observed at any visit. No significant changes were observed in P1NP concentrations. Additionally, a significant reduction from baseline was observed for NTX-1 serum levels in the Pycnogenol ® group at the end of the active-treatment extension ( p = 0.0100). Salivary M1 concentrations were significantly higher following 3 months of Pycnogenol ® supplementation compared to placebo ( p = 0.0289) and showed an inverse association with CTX-1 concentrations ( r = −0.216, p = 0.013, n = 131). Conclusion Dietary supplementation with Pycnogenol ® was associated with reductions in key bone resorption markers within the treatment group, while metabolite concentrations in saliva increased. Furthermore, Pycnogenol ® components enhanced the osteogenic differentiation of hMSCs in vitro . These findings suggest a potential protective effect of Pycnogenol ® on bone turnover in osteopenia and clinically stable osteoporosis. Clinical trial registration https://drks.de/search/de/trial/DRKS00026630 , DRKS00026630.