TY  - JOUR
A1  - Seefried, Lothar
A1  - Genest, Franca
A1  - Baumann, Jasmin
A1  - Heidemeier, Anke
A1  - Meffert, Rainer
A1  - Jakob, Franz
T1  - Efficacy of Zoledronic Acid in the Treatment of Nonmalignant Painful Bone Marrow Lesions: A Triple‐Blind, Randomized, Placebo‐Controlled Phase III Clinical Trial (ZoMARS)
JF  - Journal of Bone and Mineral Research
N2  - 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.
KW  - bone biology
KW  - osteoporosis
KW  - bone marrow lesion/edema
KW  - bisphosphonates
KW  - zoledronic acid
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276368
VL  - 37
IS  - 3
SP  - 420
EP  - 427
ER  - 
TY  - JOUR
A1  - Ebert, Regina
A1  - Weissenberger, Manuel
A1  - Braun, Clemens
A1  - Wagenbrenner, Mike
A1  - Herrmann, Marietta
A1  - Müller‐Deubert, Sigrid
A1  - Krug, Melanie
A1  - Jakob, Franz
A1  - Rudert, Maximilian
T1  - Impaired regenerative capacity and senescence‐associated secretory phenotype in mesenchymal stromal cells from samples of patients with aseptic joint arthroplasty loosening
JF  - Journal of Orthopaedic Research
N2  - Aseptic loosening of total hip and knee joint replacements is the most common indication for revision surgery after primary hip and knee arthroplasty. Research suggests that exposure and uptake of wear by mesenchymal stromal cells (MSC) and macrophages results in the secretion of proinflammatory cytokines and local osteolysis, but also impaired cell viability and regenerative capacity of MSC. Therefore, this in vitro study compared the regenerative and differentiation capacity of MSC derived from patients undergoing primary total hip arthroplasty (MSCprim) to MSC derived from patients undergoing revision surgery after aseptic loosening of total hip and knee joint implants (MSCrev). Regenerative capacity was examined by measuring the cumulative population doubling (CPD) in addition to the number of passages until cells stopped proliferating. Osteogenesis and adipogenesis in monolayer cultures were assessed using histological stainings. Furthermore, RT‐PCR was performed to evaluate the relative expression of osteogenic and adipogenic marker genes as well as the expression of markers for a senescence‐associated secretory phenotype (SASP). MSCrev possessed a limited regenerative capacity in comparison to MSCprim. Interestingly, MSCrev also showed an impaired osteogenic and adipogenic differentiation capacity compared to MSCprim and displayed a SASP early after isolation. Whether this is the cause or the consequence of the aseptic loosening of total joint implants remains unclear. Future research should focus on the identification of specific cell markers on MSCprim, which may influence complication rates such as aseptic loosening of total joint arthroplasty to further individualize and optimize total joint arthroplasty.
KW  - aseptic loosening
KW  - mesenchymal stromal cells
KW  - regenerative capacity
KW  - senescence‐associated secretory phenotype
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238963
VL  - 40
IS  - 2
SP  - 513
EP  - 523
ER  -