Impact of Intraoperative Femoral Fractures During Cemented Hemiarthroplasty for Femoral Neck Fractures.

BACKGROUND: There have been several studies on intraoperative femoral fractures (IFFs) during primary total hip arthroplasty, but it is not well understood how this complication affects the patient population undergoing cemented hemiarthroplasty. This study aimed to analyze the impact of IFFs sustained during cemented hemiarthroplasty for the treatment of femoral neck fractures. METHODS: A retrospective review was conducted of all patients who were treated for Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association 31B fractures with cemented hemiarthroplasty between January 1, 2000 and December 31, 2021, at a single academic level 1 trauma center. An initial cohort was constructed of all patients who sustained an IFF during their surgery, yielding 31 patients after excluding those who sustained a pathologic fracture or had incomplete data. These patients were matched 1:2 on age, sex, and body mass index to patients in a control cohort. The primary outcome measure was implant failure. Secondary outcome measures included complications, all-cause mortality, and radiographic outcomes (subsidence, femoral component loosening, acetabular wear, and heterotopic ossification) postoperatively. RESULTS: Subsequent implant revision was required in 3.2% (n = 1) of patients who sustained an IFF and 1.6% (n = 1) of patients who did not. After adjusting for comorbidities, there was no observed excess risk of implant failure in the fracture cohort when compared to the control cohort (hazard ratio [HR] = 0.30, P = 0.740). There was no observed excess risk of morbidity (HR = 0.69, P = 0.621) or all-cause mortality (HR = 0.23, P = 0.330). Radiographic outcomes also did not significantly differ between the 2 cohorts (P > 0.05). CONCLUSIONS: Intraoperative fractures during cemented hemiarthroplasty do not contribute to an increased risk of secondary surgery, morbidity, or mortality after surgery. They also do not adversely affect radiographic outcomes postoperatively. LEVEL OF EVIDENCE: Level III, Retrospective Comparative Study.

Cannulated Screws or Hemiarthroplasty for Femoral Neck Fractures: Is There a Mortality Difference?

OBJECTIVES: To determine the difference in mortality and reoperation rate between femoral neck fractures (FNFx) treated with cannulated screw fixation (CS) or hemiarthroplasty (HA). METHODS: Design: Retrospective study. SETTING: Institutional registry data from a single Level I trauma center. PATIENT SELECTION CRITERIA: Inclusion criteria were patients ≥60 years old with a FNFx (AO/OTA 31-B) who underwent primary operative treatment with a HA or CS. OUTCOME MEASURES AND COMPARISONS: Mortality and reoperation rates following primary operative treatment between patients treated with either hemiarthroplasty or cannulated screws. Kaplan-Meier survival curves were generated. Comparisons in the primary outcomes were made between the hemiarthroplasty or cannulated screw cohorts using univariate and multivariate analysis where appropriate. RESULTS: A total of 2,211 patients were included in the study (1,721 HA and 490 CS) and followed for an average of 34.5 months. The average age was 82.3 years (60-106 years) and predominantly female (66.3%). 1-year mortality was higher for the HA group compared to CS with a HR of 1.37 (p=0.03), however over the lifetime of patient or to final follow up, survival was not statistically significant with a RR of 0.95 95% CI, 0.83-1.1, p=0.97) The rate of reoperation at one year was lower for HA (5.0%) than for CS (10.1%), (HR 3.0, 95% CI, 2.1-4.34, p<0.0001). CONCLUSIONS: Patients with FNFx treated with hemiarthroplasty had the same risk of mortality as those patients treated with cannulated screws across lifetime of patients or until final follow up. There is no difference in mortality at the 30- and 90-day timepoint, but a significant difference in mortality at 1 year. Hemiarthroplasty treatment was associated with a significantly lower reoperation risk when compared to cannulated screws across the lifetime of the patient or until final follow up. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Morphine-induced osteolysis and hypersensitivity is mediated through toll-like receptor-4 in a murine model of metastatic breast cancer.

ABSTRACT: The propensity for breast cancer to metastasize to bone is coupled to the most common complaint among breast cancer patients: bone pain. Classically, this type of pain is treated using escalating doses of opioids, which lack long-term efficacy due to analgesic tolerance, opioid-induced hypersensitivity, and have recently been linked to enhanced bone loss. To date, the molecular mechanisms underlying these adverse effects have not been fully explored. Using an immunocompetent murine model of metastatic breast cancer, we demonstrated that sustained morphine infusion induced a significant increase in osteolysis and hypersensitivity within the ipsilateral femur through the activation of toll-like receptor-4 (TLR4). Pharmacological blockade with TAK242 (resatorvid) as well as the use of a TLR4 genetic knockout ameliorated the chronic morphine-induced osteolysis and hypersensitivity. Genetic MOR knockout did not mitigate chronic morphine hypersensitivity or bone loss. In vitro studies using RAW264.7 murine macrophages precursor cells demonstrated morphine-enhanced osteoclastogenesis that was inhibited by the TLR4 antagonist. Together, these data indicate that morphine induces osteolysis and hypersensitivity that are mediated, in part, through a TLR4 receptor mechanism.

Heat shock protein 90 inhibitors block the antinociceptive effects of opioids in mouse chemotherapy-induced neuropathy and cancer bone pain models.

Heat shock protein 90 (Hsp90) is a ubiquitous signal transduction regulator, and Hsp90 inhibitors are in clinical development as cancer therapeutics. However, there have been very few studies on the impact of Hsp90 inhibitors on pain or analgesia, a serious concern for cancer patients. We previously found that Hsp90 inhibitors injected into the brain block opioid-induced antinociception in tail flick, paw incision, and HIV neuropathy pain. This study extended from that initial work to test the cancer-related clinical impact of Hsp90 inhibitors on opioid antinociception in cancer-induced bone pain in female BALB/c mice and chemotherapy-induced peripheral neuropathy in male and female CD-1 mice. Mice were treated with Hsp90 inhibitors (17-AAG, KU-32) by the intracerebroventricular, intrathecal, or intraperitoneal routes, and after 24 hours, pain behaviors were evaluated after analgesic drug treatment. Heat shock protein 90 inhibition in the brain or systemically completely blocked morphine and oxymorphone antinociception in chemotherapy-induced peripheral neuropathy; this effect was partly mediated by decreased ERK and JNK MAPK activation and by increased protein translation, was not altered by chronic treatment, and Hsp90 inhibition had no effect on gabapentin antinociception. We also found that the Hsp90 isoform Hsp90α and the cochaperone Cdc37 were responsible for the observed changes in opioid antinociception. By contrast, Hsp90 inhibition in the spinal cord or systemically partially reduced opioid antinociception in cancer-induced bone pain. These results demonstrate that Hsp90 inhibitors block opioid antinociception in cancer-related pain, suggesting that Hsp90 inhibitors for cancer therapy could decrease opioid treatment efficacy.

Animal Models for the Study of Bone-Derived Pain.

Bone pain is a prevalent issue in society today and also is one of the hardest types of pain to control. Pain originating in the bone can be caused by many different entities including metastatic and primary neoplasm, fracture, osteoarthritis as well as numerous other metabolic disorders. In this chapter we describe the methods and protocols that currently are accepted and validated for the study of bone pain in models of metastatic cancer, bicortical fracture and osteoarthritis. These animal models provide invaluable information as to the nature of bone pain and give rise to potential new targets for its treatment and management.