Safety of Inpatient Zoledronic Acid in the Immediate Postfracture Setting.

CONTEXT: Zoledronic acid (ZA) administered during the initial hospitalization for a fragility fracture improves the osteoporosis pharmacotherapy rate. Distinguishing the safety profile of inpatient ZA (IP-ZA) in this context is crucial if this approach is to be widely adopted. OBJECTIVE: To study the acute safety profile of IP-ZA. METHODS: An observational study of patients admitted to the Massachusetts General Hospital with fragility fractures who were eligible to receive IP-ZA. Patients were treated with or without IP-ZA. Acetaminophen, either as a single pre-ZA dose or standing multiple-doses-per-day regimen for 48 hours or longer after ZA infusion, was also administered along with protocolized vitamin D and calcium supplementation. Changes in body temperature, serum creatinine, and serum calcium were measured. RESULTS: A total of 285 consecutive patients, meeting inclusion and exclusion criteria, are included in this analysis; 204 patients received IP-ZA. IP-ZA treatment was associated with a transient mean rise of body temperature of 0.31 °C on the day following its administration. Temperatures above 38 °C were seen in 15% of patients in the IP-ZA group and 4% in the nontreated group. Standing multiple-doses-per-day but not a single pre-ZA dose of acetaminophen effectively prevented this temperature increase. IP-ZA did not affect serum creatinine levels. Mean levels of serum total calcium and albumin-corrected calcium decreased by 0.54 mg/dL and 0.40 mg/dL, respectively, at their nadirs (Day 5). No patient experienced symptomatic hypocalcemia. CONCLUSION: IP-ZA along with standing multiple-doses-per-day acetaminophen, administered to patients in the immediate postfracture period, is not associated with significant acute adverse effects.

GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects.

Omega-3 fatty acids (omega-3 FAs), DHA and EPA, exert anti-inflammatory effects, but the mechanisms are poorly understood. Here, we show that the G protein-coupled receptor 120 (GPR120) functions as an omega-3 FA receptor/sensor. Stimulation of GPR120 with omega-3 FAs or a chemical agonist causes broad anti-inflammatory effects in monocytic RAW 264.7 cells and in primary intraperitoneal macrophages. All of these effects are abrogated by GPR120 knockdown. Since chronic macrophage-mediated tissue inflammation is a key mechanism for insulin resistance in obesity, we fed obese WT and GPR120 knockout mice a high-fat diet with or without omega-3 FA supplementation. The omega-3 FA treatment inhibited inflammation and enhanced systemic insulin sensitivity in WT mice, but was without effect in GPR120 knockout mice. In conclusion, GPR120 is a functional omega-3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation.

A novel synthetic androgen receptor ligand, S42, works as a selective androgen receptor modulator and possesses metabolic effects with little impact on the prostate.

We identified a novel synthetic steroid, S42, as a promising candidate of selective androgen receptor (AR) modulator. Results of the whole-cell binding assay using COS-7 cells exogenously expressing various steroid receptors indicated that S42 specifically binds to AR and progesterone receptor. When orchiectomized Sprague Dawley rats were administered with S42 for 3 wk, the muscle weight of the levator ani was increased as markedly as that induced by 5alpha-dihydrotestosterone (DHT), but the weight of the prostate was not elevated at any doses in contrast to DHT. The plasma concentrations of gonadotropin and adiponectin, those down-regulated by DHT, were unaffected by S42. In addition, although the plasma triglyceride level was unaffected by DHT, it was significantly reduced by S42. This effect of S42 was associated with suppression of the SRBP-1c-mediated lipogenic and insulin-desensitizing pathway in the liver and visceral fat. Taken together, S42 works as an AR agonist in muscle and as an AR antagonist in the prostate, pituitary gland, and liver, accompanying beneficial potentials on lipid metabolism.