Age related changes in the bone microstructure in patients with femoral neck fractures.

BACKGROUND: The risk of femoral neck fracture progressively increases with age. However, the reasons behind this consistent increase in the fracture risk can't be completely justified by the decrease in the bone mineral density. The objective of this study was to analyze the correlation between various bone structural features and age. STUDY DESIGN & METHODS: A total of 29 consecutive patients who suffered an intracapsular hip fracture and underwent joint replacement surgery between May 2012 and March 2013 were included in this study. A 2 cm × 1 cm Ø cylindrical trabecular bone sample was collected from the femoral heads and preserved in formaldehyde. Bone mineral density (BMD), microarchitecture, organic content and crystallography were analyzed using a Dual-energy X-ray absorptiometry scan, micro-CT scan, and high resolution magic-angle-spinning-nuclear magnetic resonance (MAS-NMR), respectively. Statistical correlations were made using Spearman´s or Pearson´s correlation tests depending on the distribution of the continuous variables. RESULTS: The mean patient age was 79.83 ± 9.31 years. A moderate negative correlation was observed between age and the hydrogen content in bone (1H), which is an indirect estimate to quantify the organic matrix (r = -0.512, p = 0.005). No correlations were observed between BMD, trabecular number, trabecular thickness, phosphorous content, apatite crystal size, and age (r = 0.06, p = 0.755; r = -0.008, p = 0.967; r = -0.046, p = 0.812; r = -0.152, p = 0.430, respectively). A weak positive correlation was observed between Charlson´s comorbidity index (CCI) and c-axis of the hydroxiapatite (HA) crystals (r = -0.400, p = 0.035). CONCLUSION: The femoral head relative protein content progressively decreases with age. BMD was not correlated with other structural bone parameters and age. Patients with higher comorbidity scores had larger HA crystals. The present results suggest that the progressive increase in the hip fracture risk in elderly patients could be partially explained by the lower bone protein content in this age group.

Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery.

Postoperative pain relief is crucial for full recovery. With the ongoing opioid epidemic and the insufficient effect of acetaminophen on severe pain; non-steroidal anti-inflammatory drugs (NSAIDs) are heavily used to alleviate this pain. However, NSAIDs are known to inhibit postoperative healing of connective tissues by inhibiting prostaglandin signaling. Pain intensity, inflammatory mediators associated with wound healing and the pharmacological action of NSAIDs vary throughout the day due to the circadian rhythm regulated by the clock genes. According to this rhythm, most of wound healing mediators and connective tissue formation occurs during the resting phase, while pain, inflammation and tissue resorption occur during the active period of the day. Here we show, in a murine tibia fracture surgical model, that NSAIDs are most effective in managing postoperative pain, healing and recovery when drug administration is limited to the active phase of the circadian rhythm. Limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, such as Period 2 (Per2) at the healing callus, and increased serum levels of anti-inflammatory cytokines interleukin-13 (IL-13), interleukin-4 (IL-4) and vascular endothelial growth factor. By contrast, NSAID administration during the resting phase resulted in severe bone healing impairment.