@article{GenestRakPetryketal.2020,
  author    = {Genest, Franca and Rak, Dominik and Petryk, Anna and Seefried, Lothar},
  title     = {Physical Function and Health-Related Quality of Life in Adults Treated With Asfotase Alfa for Pediatric-Onset Hypophosphatasia},
  series = {JBMR Plus},
  volume    = {4},
  journal   = {JBMR Plus},
  number    = {9},
  doi       = {10.1002/jbm4.10395},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218410},
  year      = {2020},
  abstract  = {Hypophosphatasia (HPP) is a rare, inherited, metabolic disease characterized by tissue-nonspecific alkaline phosphatase deficiency resulting in musculoskeletal and systemic clinical manifestations. This observational study evaluated the effectiveness of enzyme replacement therapy with asfotase alfa on physical function and health-related quality of life (HRQoL) among adults with pediatric-onset HPP who received asfotase alfa for 12 months at a single center (ClinicalTrial.gov no.: NCT03418389). Primary outcomes evaluated physical function with the 6-minute walk test (6MWT), timed up-and-go (TUG) test, Short Physical Performance Battery (SPPB), and handheld dynamometry (HHD). Secondary outcome measures included the Lower Extremity Functional Scale (LEFS), pain prevalence/intensity, and pain medication use; HRQoL was evaluated using the 36-Item Short-Form Health Survey version 2 (SF-36v2). Safety data were collected throughout the study. All 14 patients (11 women) had compound heterozygous ALPL gene mutations and ≥1 HPP bone manifestation, including history of ≥1 fracture. Mean (min, max) age was 51 (19 to 78) years. From baseline to 12 months of treatment, median 6MWT distance increased from 267 m to 320 m (n = 13; p = 0.023); median TUG test time improved from 14.4 s to 11.3 s (n = 9; p = 0.008). Specific components of the SPPB also improved significantly: median 4-m gait speed increased from 0.8 m/s to 1.1 m/s (n = 10; p = 0.007) and median repeated chair-rise time improved from 22 s to 13 s (n = 9; p = 0.008). LEFS score improved from 24 points to 53 points (n = 10; p = 0.002). Improvements in HHD were not clinically significant. SF-36v2 Physical Component Score (PCS) improved after 12 months of treatment (n = 9; p = 0.010). Pain level did not change significantly from baseline to 12 months of treatment. There were significant improvements on chair-rise time and SF-36v2 PCS by 3 months, and on TUG test time after 6 months. No new safety signals were identified. These results show the real-world effectiveness of asfotase alfa in improving physical functioning and HRQoL in adults with pediatric-onset HPP. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.},
  language  = {en}
}
@article{JessbergerHoeggerGenestetal.2017,
  author    = {Jessberger, Steffen and H{\"o}gger, Petra and Genest, Franca and Salter, Donald M. and Seefried, Lothar},
  title     = {Cellular pharmacodynamic effects of Pycnogenol\(^{®}\) in patients with severe osteoarthritis: a randomized controlled pilot study},
  series = {BMC Complementary and Alternative Medicine},
  volume    = {17},
  journal   = {BMC Complementary and Alternative Medicine},
  number    = {537},
  doi       = {10.1186/s12906-017-2044-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159532},
  year      = {2017},
  abstract  = {Background: 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. Methods: 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. Results: 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. Conclusions: 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.},
  language  = {en}
}