The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies.

INTRODUCTION: Osteoporosis is characterised by low bone mass and micro-architectural deterioration of bone structure. Its treatment is directed at the processes of bone formation or resorption, that are of utmost importance in fracture healing. We provide a comprehensive review of the literature aiming to summarize and clarify the effects of osteoporosis and its treatment on fracture healing. MATERIAL AND METHODS: A literature search was conducted in PubMed and Embase (OVID version). In vivo animal and human studies on long bone fractures were included. A total of 93 articles were included for this review; 23 studies on the effect of osteoporosis (18 animal and 5 clinical studies) and 70 studies on the effect of osteoporosis treatment (41 animal, 26 clinical studies and 3 meta-analyses) on fracture healing. RESULTS: In animal fracture models osteoporosis was associated with decreased callus formation and bone growth, bone mineral density, biomechanical strength and delayed cellular and differentiation processes during fracture healing. Two large databases identified osteoporosis as a risk factor for non-union whereas three other studies did not. One of those three studies however found a prolonged healing time in patients with osteoporosis. Anti-osteoporosis medication showed inconsistent effects on fracture healing in both non-osteoporotic and osteoporotic animal models. Only the parathyroid hormone and anti-resorption medication were related to improved fracture healing and delayed remodelling respectively. Clinical studies performed in predominantly hip and distal radius fracture patients showed no effect of bisphosphonates on fracture healing. Parathyroid hormone reduced time to union in several clinical trials performed in mainly hip fracture patients, but this did not result in decreased delayed or non-union rates. CONCLUSION: Evidence that substantiates the negative influence of osteoporosis on fracture healing is predominantly from animal studies and to a lesser extent from clinical studies, since convincing clinical evidence lacks. Bisphosphonates and parathyroid hormone may be used during fracture healing, since no clear negative effect has been shown. Parathyroid hormone might even decrease time to fracture union, without decreasing union rate.

Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite.

Denitrifying bacteria in soil generate nitric oxide (NO) from nitrite as a part of the nitrogen cycle, but little is known about NO production by commensal bacteria. We used a chemiluminescence assay to explore if human faeces and different representative gut bacteria are able to generate NO. Bacteria were incubated anaerobically in gas-tight bags, with or without nitrate or nitrite in the growth medium. In addition, luminal NO levels were measured in vivo in the intestines in germ-free and conventional rats, and in rats mono-associated with lactobacilli. We show that human faeces can generate NO after nitrate or nitrite supplementation. Lactobacilli and bifidobacteria generated much NO from nitrite, but only a few of the tested strains produced NO from nitrate and at much lower levels. In contrast, Escherichia coli, Bacteroides thetaiotaomicron, and Clostridium difficile did not produce significant amounts of NO either with nitrate or nitrite. NO generation in the gut lumen was also observed in vivo in conventional rats but not in germ-free rats or in rats mono-associated with lactobacilli. We conclude that NO can be generated by the anaerobic gut flora in the presence of nitrate or nitrite. Future studies will reveal its biological significance in regulation of gastrointestinal integrity.

Effect of intravenous L-NMMA on nitric oxide production in collagenous colitis.

BACKGROUND: Nitric oxide (NO) is greatly increased in the colon of patients with inflammatory bowel disease of different aetiology, including collagenous colitis. In man, NO can be generated from NO synthases as well as from non-enzymatic sources. The source of the NO found in luminal intestinal gas has not been exactly pinpointed. We investigated the effect of the NO synthase inhibitor L-NMMA on intestinal concentrations of NO in patients with clinically active collagenous colitis. In addition, we measured NO levels from the respiratory tract. METHODS: Ten patients with active collagenous colitis were studied. NO levels were measured from the respiratory tract and in the rectum before and after i.v. administration of L-NMMA (7.5 mg/kg) using a chemiluminescence method. RESULTS: Airway NO release decreased markedly, and mean arterial blood pressure increased in all patients following L-NMMA treatment. Basal rectal NO levels were high (median > 10000 ppb) and decreased markedly in 5 patients after L-NMMA. In contrast, NO levels remained completely unchanged or even increased in the other 5 patients. CONCLUSION: Rectal levels of NO are greatly increased in patients with symptomatic collagenous colitis. Intravenous administration of an NO synthase inhibitor reduced rectal NO only in half of the patients despite clear evidence of effective systemic NO synthase inhibition. This could indicate alternative NOS-independent sources of intestinal NO in this disease.

Sensitive gas chromatographic determination of the cyclophosphamide metabolite 2-dechloroethylcyclophosphamide in human plasma.

Cyclophosphamide (CP) is one of the most frequently used anticancer agents. It is a prodrug requiring activation before exerting cytotoxicity. CP is deactivated to 2-dechloroethylcyclophosphamide (2-DCECP) with formation of an equimolar amount of chloroacetaldehyde. The aim of this study was to develop and validate a sensitive and simple assay for 2-DCECP in plasma of patients treated with CP. Sample pre-treatment consisted of solid-phase extraction of 500 microl of plasma over OASIS HLB (1 ml) cartridges with trofosfamide as internal standard. Separation and detection of underivatized 2-DCECP was performed with capillary gas chromatography with nitrogen/phosphorous selective detection. Extraction recovery of 2-DCECP exceeded 87%. No interference from endogenous compounds, other metabolites of CP and frequently coadministered drugs was detected. The assay was linear in the range of 5-5000 ng/ml in plasma. Accuracy, within-day and between-day precision were less than 11% for the complete concentration range. In plasma, 2-DCECP was stable for at least 1 month when kept at -70 degrees C. Analysis of samples from patients treated with CP demonstrated the applicability of the assay. In conclusion, a sensitive and simple assay for 2-DCECP in plasma, which meets the current requirements for bioanalytical assays, was developed.

[Glass ionomer cement used as a retrograde filling material after apicoectomy: a review]. / Glasionomeercement als retrograde vulling bij apexresecties.

When an apicoectomy is performed, using retrograde sealing with amalgam, the healing of the periapical area is not always perfect. In a number of cases the cause of this imperfect healing may be due to the improper sealing ability and the moderate tissue compatibility of amalgam. A literature study has been carried out, based on the assumption that glass ionomer cement will provide a better sealing and will cause less tissue reaction. It appeared that, at least in theory, glass ionomer cement is to be preferred to amalgam when it comes to apical sealing properties and tissue reaction. In terms of usability, resorption, hardness and costs no significant differences were found. The conclusion is drawn that glass ionomer cement is an equal or perhaps even better alternative for retrograde amalgam.