ABSTRACTPurposeNonsteroidal anti-inflammatory drugs (NSAID) are associated with increased stress fracture risk, potentially due to inhibiting the adaptive bone formation responses to exercise. This study investigated if a single, maximal dose of three different NSAID alters bone formation biomarker response to strenuous exercise.MethodsIn a randomized, counterbalanced order, 12 participants (10 male, 2 female), performed four bouts of plyometric jumps, each separated by at least 1 wk. Two hours before exercise, participants consumed either placebo or NSAID: ibuprofen (800 mg), celecoxib (200 mg), flurbiprofen (100 mg). Blood was collected before (PRE), and at 0, 15, 60, 120, and 240 min postexercise. Parathyroid hormone, ionized calcium, procollagen type 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin, C-terminal telopeptide of type 1 collagen, tartrate-resistant acid phosphatase, and sclerostin were measured. Prostaglandin E2 metabolite and creatinine were measured in urine. Data were analyzed using repeated-measures ANOVA and area under the curve analysis. Data are mean ± SD.ResultsThere was an exercise effect for procollagen type 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin, C-terminal telopeptide of type 1 collagen, tartrate-resistant acid phosphatase, sclerostin, osteoprotegerin, parathyroid hormone, and ionized calcium (all P < 0.05), but no NSAID treatment effect for any biomarker (all P > 0.05). Area under the curve analyses were not different for any biomarker (P > 0.05). Prostaglandin E2 metabolite was higher during the placebo trial (322 ± 153 pg·mg−1 creatinine, P < 0.05) compared with ibuprofen (135 ± 83 pg·mg−1), celecoxib (202 ± 107 pg·mg−1), and flurbiprofen (159 ± 74 pg·mg−1).ConclusionsPlyometric exercise induced changes in bone metabolism, but the responses were unaltered by consuming NSAID 2 h before exercise.

01 Nov 2024·International Journal of Pharmaceutics

Formulation, optimization and evaluation of ibuprofen loaded menthosomes for transdermal delivery

Article

Author: Gopinathan, Adarsh ; Rathnanand, Mahalaxmi ; John, Jeena ; Halagali, Praveen ; Shetty, Manisha M ; Nayak, Devika ; Krishna Tippavajhala, Vamshi

The study aimed to improve the transdermal permeation of IBU utilizing menthosomes as a vesicular carrier. IBU-loaded menthosomes were formulated by thin film hydration & optimized using 2³ factorial designs (Design Expert® version 13 software). In vitro & ex vivo skin permeation analysis of IBU-encapsulated menthosomes was studied across the rat skin sample. In vivo pharmacodynamic activity was studied in an arthritis rat model. The optimized IBU-loaded menthosomes exhibited an optimum vesicle size of 214.2 ± 2.96 nm, Zeta potential of -21.1 ± 2.72 mV, (PDI) Polydispersity Index of 0.267 ± 0.018 with Entrapment efficiency (EE%) of 78.7 ± 2.73 %. The in vitro & ex vivo skin penetration study displayed enhanced release of drug of 77.02 ± 1.0 % and 40.91 ± 0.81 % respectively, compared to conventional liposomes. In vivo pharmacodynamic study on carrageenan-induced paw edema in Wistar albino rats demonstrated superior anti-inflammatory activity of the optimized IBU-encapsulated menthosomes (**p < 0.01) and effective inhibition of paw edema (34.04 ± 0.155 %). The formalin test indicated a significant analgesic effect of optimized formulation during the chronic phase of analgesia (*p < 0.05) compared to the control group. Thus, the developed and optimized drug-loaded menthosomes could serve as a suitable vesicular delivery carrier in enhancing the transdermal delivery of other NSAID drugs.

01 Sep 2024·The Journal of Arthroplasty

The Use of Tranexamic Acid for Primary Prophylaxis of Heterotopic Ossification Following Total Hip Arthroplasty

Article

Author: King, Paul J ; Johnson, Andrea H. ; Turcotte, Justin J ; Brennan, Jane C ; Brennan, Jane C. ; Turcotte, Justin J. ; Johnson, Andrea H ; King, Paul J. ; Rana, Parimal

BACKGROUNDHeterotopic ossification (HO) is a relatively common complication after total hip arthroplasty (THA) and can range from a radiographic observation only to severely disabling and requiring revision surgery. Prophylaxis is recommended for high-risk patients, though the ideal method and targeted population are open to debate. Tranexamic acid (TXA) is a medication increasingly being used to reduce blood loss associated with orthopaedic surgeries, including THA.METHODSA retrospective review of 357 patients undergoing THA from November 2020 through December 2023 was conducted. The patients were grouped based on whether they received intravenous TXA perioperatively or not, and their propensity score matched 2:1 TXA to no TXA on age, body mass index, sex, Charlson Comorbidity Index, and perioperative celecoxib use. Univariate and multivariate analyses were performed.RESULTSAfter propensity score matching, the only significant differences between groups were American Society of Anesthesiologists (ASA) scores and preoperative celecoxib use between groups, as the TXA group had fewer patients who had an ASA of 3 or more (38.9 versus 58.5%, P < 0.001) and more patients who had taken celecoxib preoperatively (16.3 versus 5.9%, P = 0.010). Perioperatively, patients were more likely to undergo THA using the anterior approach (74.5 versus 57.6%, P = 0.002) and were more likely to receive postoperative celecoxib prescriptions (44.8 versus 31.4%, P = 0.021), but there was no difference in other nonsteroidal anti-inflammatory drug (NSAID) usage postoperatively. Postoperatively, patients who received TXA had a lower rate of HO on the last postoperative x-ray (20.1 versus 33.9%, P = 0.007). Multivariable logistic regression, to assess predictors of HO, found that patients who had TXA were 42% less likely to have visible HO (OR [odds ratio] = 0.58, P = 0.047), while holding surgical approach, American Society of Anesthesiologists score, preoperative and postoperative celecoxib use, and postoperative other nonsteroidal anti-inflammatory drug use constant.CONCLUSIONSThe use of TXA in patients undergoing primary THA results in a decreased likelihood ofHO formation on postoperative x-rays.

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Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Preclinical	IT	University of Turin	11 Oct 2001

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