The present randomized controlled study aimed to investigate the in vivo distribution of constituents or metabolites of the standardized maritime pine bark extract Pycnogenol^®. Thirty-three patients with severe osteoarthritis scheduled for a knee arthroplasty were randomized to receive either 200 mg per day Pycnogenol^® (P+) or no treatment (Co) over three weeks before surgery. Serum, blood cells, and synovial fluid samples were analyzed using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization (LC-ESI/MS/MS). Considerable interindividual differences were observed indicating pronounced variability of the polyphenol pharmacokinetics. Notably, the highest polyphenol concentrations were not detected in serum. Catechin and taxifolin primarily resided within the blood cells while the microbial catechin metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone, ferulic, and caffeic acid were mainly present in synovial fluid samples. Taxifolin was detected in serum and synovial fluid exclusively in the P+ group. Likewise, no ferulic acid was found in serum samples of the Co group. Calculating ratios of analyte distribution in individual patients revealed a simultaneous presence of some polyphenols in serum, blood cells, and/or synovial fluid only in the P+ group. This is the first evidence that polyphenols distribute into the synovial fluid of patients with osteoarthritis which supports rationalizing the results of clinical efficacy studies.

The standardized maritime pine bark extract (Pycnogenol®) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol® and its in vivo mechanism of action in OA patients. Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol® twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients’ chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples. The oral intake of Pycnogenol® downregulated the gene expression of various cartilage degradation markers in the patients’ chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract. This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol® on symptom scores of patients suffering from OA. ISRCTN10754119 . Retrospectively registered 08/10/2015.

Bone marrow lesions (BML) represent areas of deteriorated bone structure and metabolism characterized by pronounced water-equivalent signaling within the trabecular bone on magnetic resonance imaging (MRI). BML are associated with repair mechanisms subsequent to various clinical conditions associated with inflammatory and non-inflammatory injury to the bone. There is no approved treatment for this condition. Bisphosphonates are known to improve bone stability in osteoporosis and other bone disorders and have been used off-label to treat BML. A randomized, triple-blind, placebo-controlled phase III trial was conducted to assess efficacy and safety of single-dose zoledronic acid (ZOL) 5 mg iv with vitamin D 1000 IU/d as opposed to placebo with vitamin D 1000 IU/d in 48 patients (randomized 2:1) with BML. Primary efficacy endpoint was reduction of edema volume 6 weeks after treatment as assessed by MRI. After treatment, mean BML volume decreased by 64.53% (±41.92%) in patients receiving zoledronic acid and increased by 14.43% (±150.46%) in the placebo group (p = 0.007). A decrease in BML volume was observed in 76.5% of patients receiving ZOL and in 50% of the patients receiving placebo. Pain level (visual analogue scale [VAS]) and all categories of the pain disability index (PDI) improved with ZOL versus placebo after 6 weeks but reconciled after 6 additional weeks of follow-up. Six serious adverse events occurred in 5 patients, none of which were classified as related to the study drug. No cases of osteonecrosis or fractures occurred. Therefore, single-dose zoledronic acid 5 mg iv together with vitamin D may enhance resolution of bone marrow lesions over 6 weeks along with reduction of pain compared with vitamin D supplementation only. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Aging is associated with progressive loss of musculoskeletal performance. Exercise interventions can improve physical function in the elderly but there is a paucity of comparative assessments in order to understand what specific goals can be achieved particularly with less demanding exercise interventions readily accessible for untrained men. Prospective randomized, controlled, single center exploratory trial to compare four distinct exercise interventions, i.e. Resistance Training (RT), Whole Body Vibration Exercise (WBV), Qi Gong (QG) and wearing a Spinal orthosis (SO) for 6 months in men at risk for osteoporosis aged 65–90 years. Primary endpoint was change in isometric one repetition maximum force trunk strength for extension (TSE) and flexion (TSF) compared to baseline, secondary endpoints covered key parameters of geriatric functional assessment, including Handgrip Strength (HS), Chair-Rise-Test (CRT), Usual Gait Speed (UGS) and Timed-Up-and-Go (TUG). Altogether 47 men (mean age 77 ±6.1 years) were randomized to RT, (n = 11) WBV (n = 13), QG (n = 10) and SO(n = 13). RT, defined as reference exercise intervention, lead to significant improvements for TSE (p = 0.009) and TSF (p = 0.013) and was significantly superior in the between-group analysis for TSE (p = 0.038). Vibration exercise caused sign. Improvements in TSE (p = 0.014) and CRT (p = 0.005), the Spinal orthosis improved CRT (p = 0.003) and Gait Speed (p = 0.027), while the QG intervention did not attain any sig. Developments. Subgroup analyses revealed most pronounced musculoskeletal progress in vulnerable patients (age ≥ 80 years, pre-sarcopenia, multimorbidity ≥3chronic diseases). Irrespective of the type of exercise, participants ≥80 years experienced significant gains in TSE (p = 0.029) and CRT (p = 0.017). Presarcopenic subjects (Skeletal muscle Index (SMI) ≤10.75 kg/m²) improved in TSE (p = 0.003), CRT (p = 0.001) and UGS (p = 0.016). Multimorbid participants achieved sig. Gains in TSE (p < 0.001), TSF (p = 0.002), UGS (p = 0.036) and HS (p = 0.046). In this exploratory trial we found that simple exercise interventions are feasible in elderly men eliciting specific benefits, i.e. improvements are attained in those tasks addressed with the respective exercise modality. While targeted resistance training is superior in increasing TSE, alternative simple exercise interventions also appear to elicit beneficial effects, even in vulnerable patients, i.e. those with low muscle mass, above 80 years of age or multimorbidity.

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a risk factor for reduced physical performance, osteoporosis, and fractures due to compromised musculoskeletal metabolism. In this condition it is unknown whether whole-body vibration (WBV) exercise favorably alters physical performance and bone metabolism. To evaluate the effect of three-months WBV exercise (30 min; 2x/week) including an optional three-month extension on physical performance, bone metabolism and bone mineral density. Endpoints included functional assessments, bone turnover markers and bone mineral density assessed by peripheral quantitative computed tomography of the tibia. Fifteen MGUS patients (median age 62.0, nine female) completed the first three months of which ten completed the three-month extension. Measures of physical functioning including chair rise test, timed up and go and 6-minute walk test improved (p = 0.007; p = 0.009; p = 0.005) after three and six months of WBV exercise. Total tibial bone mineral density remained unaltered (p > 0.05). WBV exercise tended to increase levels of sclerostin (p = 0.093) with a transient increase in osteoclast resorption markers (N-terminal telopeptide of collagen type 1, tartrate resistant acid phosphatase 5b) after three months while Dickkopf-1 (p = 0.093), procollagen I N-terminal propeptide (p = 0.074) and total alkaline phosphatase (p = 0.016) appeared to decline. No exercise-related adverse events were reported. WBV exercise in MGUS patients improves indicators of physical performance. Observed trends in bone turnover markers and changes in distal tibial bone mineral density may indicate a regulatory effect of WBV exercise on bone metabolism and warrants further evaluation by large scale studies.