The role of biomechanics and inflammation in cartilage injury and repair

Osteoarthritis is a painful and debilitating disease characterized by progressive degenerative changes in the articular cartilage and other joint tissues. Biomechanical factors play a critical role in the initiation and progression of this disease, as evidenced by clinical and animal studies of alterations in the mechanical environment of the joint caused by trauma, joint instability, disuse, or obesity. The onset of these changes after joint injury generally has been termed posttraumatic arthritis and can be accelerated by factors such as a displaced articular fracture. Within this context, there is considerable evidence that interactions between biomechanical factors and proinflammatory mediators are involved in the progression of cartilage degeneration in posttraumatic arthritis. In vivo studies have shown increased concentrations of inflammatory cytokines and mediators in the joint in mechanically induced models of osteoarthritis. In vitro explant studies confirm that mechanical load is a potent regulator of matrix metabolism, cell viability, and the production of proinflammatory mediators such as nitric oxide and prostaglandin E2. Knowledge of the interaction of inflammatory and biomechanical factors in regulating cartilage metabolism would be beneficial to an understanding of the etiopathogenesis of posttraumatic osteoarthritis and in the improvement of therapies for joint injury.     

Pilot study of a novel pain management strategy: evaluating the impact on patient outcomes

Background

Our objective was to evaluate the impact of a novel multimodal pain management strategy on intraoperative opioid requirements, postoperative pain, narcotic use, and length of stay.

Methods

Consecutive patients undergoing elective laparoscopic colorectal resection were managed with an experimental protocol. The protocol uses a post-induction, pre-incision bilateral TAP block and local peritoneal infiltration at port sites with long-acting liposomal bupivacaine (20 mL long-acting liposomal bupivacaine, 30 mL 0.25 % bupivacaine, 30 mL saline). Experimental patients were matched on age, body mass index, gender, comorbidity, diagnosis, and procedure to a control group that received no block or local wound infiltration. Both groups followed a standardized enhanced recovery pathway. Demographics, perioperative, and postoperative outcomes were evaluated. The main outcome measures were intraoperative opioids, postoperative pain, opioid use, and length of stay.

Results

Fifty patients were analyzed—25 experimental and 25 controls. Patients were well matched on all demographics. In both cohorts, the main diagnosis was colorectal cancer and primary procedure performed a segmental resection. Operative times were similar (p = 0.41). Experimental patients received significantly less intraoperative fentanyl (mean 158 mcg experimental vs. 299 mcg control; p < 0.01). The experimental group had significantly lower initial (p < 0.01) and final PACU pain scores (p = 0.04) and shorter LOS (3.0 vs. 4.1 days, p = 0.04) compared to controls. Experimental patients trended toward shorter PACU times and lower opioid use and daily pain scores throughout the hospital stay. Postoperative complication and readmission rates were similar across groups. There were no reoperations or mortality.

Conclusions

Our multimodal pain management strategy reduced intraoperative opioid administration. Postoperatively, improvements in PACU time, postoperative pain and narcotic use, and lengths of stay were seen in the experimental cohort. With the favorable finding from the pilot study, further investigation is warranted to fully evaluate the impact of this pain management protocol on patient satisfaction, clinical and financial outcomes.

     

The effect of staged decompression while breathing 100% oxygen on altitude decompression sickness

INTRODUCTION: Space Shuttle extravehicular activity (EVA) requires decompression from sea level pressure (14.7 psia) to a 4.3 psia (30,300 ft) pressure suit. The transition currently involves altering the shuttle atmosphere to allow shirt-sleeve denitrogenation to occur during a 12 to 36-h staged decompression (SD) at 10.2 psia (9,800 ft) with an oxygen-enriched breathing gas (26.5% oxygen, 73.5% nitrogen). The denitrogenation provides protection from decompression sickness (DCS) during EVA in a 4.3 psia pressure suit. Our goal was to determine the highest altitude at which SD while breathing 100% oxygen (SD100) could provide effective protection from development of DCS symptoms after further decompression to 29,500 ft (4.5 psia). METHODS: There were 30 male subjects exposed to at least 6 of 11 conditions in random order on successive months to 29,500 ft for 4 h while performing mild exercise and being monitored for venous gas emboli (VGE) with an echo-imaging system. The subjects received 15 min of ground-level (GL) preoxygenation and an additional 60 or 120 min of SD100 at one of four altitudes between 8,000 ft (10.9 psia) and 18,000 ft (7.3 psia). Control exposures followed a 75- or 135-min ground-level preoxygenation. RESULTS: During SD100, one case of DCS occurred at 18,000 ft, but not at lower staging altitudes. Higher levels of VGE were observed during SD100 at 18,000 ft than during SD100 at any lower altitude. CONCLUSION: Staged decompression at 16,000 ft and below results in decompression risk during subsequent decompression to 29,500 ft similar to that following equivalent periods of ground-level preoxygenation.     

Osteonecrosis of jaw in patient with hormone-refractory prostate cancer treated with zoledronic acid

Intravenous bisphosphonates are widely used in the management of metastatic bone disease, as well as osteoporosis. Recent published reports have documented a possible link between treatment with intravenous bisphosphonates and osteonecrosis of the jaw. We report a case of osteonecrosis of the jaw in 1 patient with prostate cancer receiving both chemotherapy and intravenous zoledronic acid (Zometa). Bisphosphonates have been demonstrated to alter the normal bone microenvironment and appear to have direct effects on tumors as well. These changes may contribute to the development of osteonecrosis of the jaw, particularly after tooth extractions or other invasive dental procedures.     

The prevalence and significance of low preoperative hemoglobin in ASA 1 or 2 outpatient surgery candidates

Asymptomatic anemia in healthy patients undergoing low risk surgery is rare. In this retrospective study, we examined the records of 9584 ASA class I-II patients scheduled for elective low risk surgery who had a preoperative hemoglobin (hgb) test for the presence of anemia. Hgb <9 g/dL was detected in 75 patients (0.8%). Perioperative management of anemia occurred in no cases of elective surgery in this group. Transfusion of red cells occurred in four other patients, all of whom had hgb >9 g/dL. In all cases, management decisions were based on clinical factors rather than the preoperative hemoglobin test. In healthy patients undergoing low risk elective surgery, routine preoperative hgb testing is not indicated.     

Effects of salmon calcitonin on trabecular microarchitecture as determined by magnetic resonance imaging: results from the QUEST study.

The unique noninvasive MRI technique was used to assess trabecular microarchitecture at multiple skeletal sites in 91 postmenopausal osteoporotic women receiving nasal spray salmon calcitonin (CT-NS) or placebo over 2 years. In the distal radius and lower trochanter of the hip, individuals treated with CT-NS exhibited significant preservation of trabecular bone microarchitecture compared with placebo, where significant deterioration was shown. MRI analyses of os calcis or microCT/histomorphometric analyses of bone biopsies did not reveal consistent differences in architecture between CT-NS and placebo. INTRODUCTION: It is postulated that the reduction in osteoporotic fracture risk in response to certain antiresorptive osteoporosis therapies is caused less by effects on bone quantity than on bone quality (specifically trabecular microarchitecture). To test this hypothesis, the QUEST study was conducted to assess the effects of nasal spray salmon calcitonin (CT-NS) or placebo on parameters of trabecular microarchitecture at multiple skeletal sites using noninvasive MRI technology and iliac crest bone biopsies by microCT/histomorphometry. MATERIALS AND METHODS: Ninety-one postmenopausal osteoporotic women were followed for 2 years (n = 46 for CT-NS, n = 45 for placebo); all women received 500 mg calcium daily. MRI measurements at distal radius, hip (T2 relaxation time [T2*]), and os calcis (obtained yearly), iliac crest bone biopsies with 2D histomorphometry and 3D microCT (obtained at study onset and conclusion), DXA-BMD at spine/hip/wrist/os calcis (obtained yearly), and markers of bone turnover (obtained at 2-week to 12-month intervals) were analyzed, with an analysis of covariance model used to assess treatment effect for parameters of interest. RESULTS AND CONCLUSIONS: MRI assessment of trabecular microarchitecture at individual regions of the distal radius revealed significant improvement, or preservation (no significant loss), in the CT-NS-treated group compared with significant deterioration in the placebo control group, as reflected in apparent BV/TV (p < 0.03), apparent trabecular number (p < 0.01), and apparent trabecular spacing (p < 0.01). Also, at the hip, the CT-NS group exhibited preservation of trabecular microarchitecture at the lower trochanter (p < 0.05) as determined by T2* MRI technology. Significant deterioration of trabecular bone architecture was noted in the placebo group at the femoral neck, Ward's triangle, and lower trochanteric sites. Apart from a significant increase in apparent trabecular number in the CT-NS group, significant changes within or between groups were not noted at the os calcis. Combined microCT/histomorphometric analysis of iliac crest bone biopsies did not reveal significant differences between treated and placebo groups. In the CT-NS group, regardless of the change in BMD (gain or loss) at the spine, hip, or distal radius, preservation of parameters of trabecular microarchitecture was noted, whereas in the placebo group, regardless of the change in BMD (gain or loss) at the spine, hip, or distal radius, loss or preservation was noted; however, changes in DXA/BMD (of the spine, hip, wrist, os calcis) between CT-NS and placebo groups were not significant. Serum C-telopeptide (S-CTx), a specific bone resorption marker, was reduced by 22.5% at 24 months (p = 0.056). The results of the QUEST study suggest therapeutic benefit of CT-NS compared with placebo in maintaining trabecular microarchitecture at multiple skeletal sites and support the use of MRI technology for assessment of trabecular microarchitecture in clinical research trials. However, the results also highlight site specific differences in response to antiresorptive therapies and the importance of sufficiently large sampling volumes (areas) to obtain reliable assessment of bone architecture.     

Excess mortality following hip fracture: a systematic epidemiological review

Summary This systematic literature review has shown that patients experiencing hip fracture after low-impact trauma are at considerable excess risk for death compared with nonhip fracture/community control populations. The increased mortality risk may persist for several years thereafter, highlighting the need for interventions to reduce this risk. Patients experiencing hip fracture after low-impact trauma are at considerable risk for subsequent osteoporotic fractures and premature death. We conducted a systematic review of the literature to identify all studies that reported unadjusted and excess mortality rates for hip fracture. Although a lack of consistent study design precluded any formal meta-analysis or pooled analysis of the data, we have shown that hip fracture is associated with excess mortality (over and above mortality rates in nonhip fracture/community control populations) during the first year after fracture ranging from 8.4% to 36%. In the identified studies, individuals experienced an increased relative risk for mortality following hip fracture that was at least double that for the age-matched control population, became less pronounced with advancing age, was higher among men than women regardless of age, was highest in the days and weeks following the index fracture, and remained elevated for months and perhaps even years following the index fracture. These observations show that patients are at increased risk for premature death for many years after a fragility-related hip fracture and highlight the need to identify those patients who are candidates for interventions to reduce their risk.     

The EMG of conventional abdominal exercise and exercise with a semi-upright commercial device: comparative effects and technique considerations

AIM: The purpose of this study was to measure and compare the muscle activity of the rectus abdominis (RA) and external obliques (EO) with conventional exercises and while using an upright commercial abdominal training device (the CoreMaster). It was hypothesized that the upright device would elicit higher electromyography (EMG) values compared to conventional abdominal exercises. METHODS: Fifteen subjects (8 males, 7 females) participated in this study. Each subject performed 10 repetitions for 5 exercises: truck lift (TL); trunk rotation to opposite knee (TROK); trunk lift on the CoreMaster (TLCM); trunk rotation on the CoreMaster (TRCM); and trunk rotation with a leg lift on the CoreMaster (TRLLCM). Muscle activity was measured for the RA and EO using surface EMG. A Biopac system (Goleta, CA, USA) processed the EMG signals. A repeated measures analysis of variance (ANOVA) determined any difference in the root mean square values and Bonferroni comparisons were used to clarify the order of differences (P<0.05). RESULTS: For the RA, all exercises on the CoreMaster produced significantly higher EMG values compared to the conventional TL. For the EO, TRCM elicited the highest EMG values. However, no significant difference was found for EO between TROK and TRLLCM. CONCLUSION: The CoreMaster elicited a greater challenge to the RA. For the EO, the CoreMaster yielded optimal effects for exercises that required pronounced rotation.     

Salmon calcitonin: a review of current and future therapeutic indications

Salmon calcitonin, available as a therapeutic agent for more than 30 years, demonstrates clinical utility in the treatment of such metabolic bone diseases as osteoporosis and Paget's disease, and potentially in the treatment of osteoarthritis. This review considers the physiology and pharmacology of salmon calcitonin, the evidence based research demonstrating efficacy and safety of this medication in postmenopausal osteoporosis with potentially an effect on bone quality to explain its abilities to reduce the risk of spine fracture, the development of an oral salmon calcitonin preparation, and the therapeutic rationale for this preparation's chondroprotective effect in osteoarthritis.