Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis.

Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.

Hox genes are crucial regulators of periosteal stem cell identity.

Periosteal stem and progenitor cells (PSPCs) are major contributors to bone maintenance and repair. Deciphering the molecular mechanisms that regulate their function is crucial for the successful generation and application of future therapeutics. Here, we pinpoint Hox transcription factors as necessary and sufficient for periosteal stem cell function. Hox genes are transcriptionally enriched in periosteal stem cells and their overexpression in more committed progenitors drives reprogramming to a naïve, self-renewing stem cell-like state. Crucially, individual Hox family members are expressed in a location-specific manner and their stem cell-promoting activity is only observed when the Hox gene is matched to the anatomical origin of the PSPC, demonstrating a role for the embryonic Hox code in adult stem cells. Finally, we demonstrate that Hoxa10 overexpression partially restores the age-related decline in fracture repair. Together, our data highlight the importance of Hox genes as key regulators of PSPC identity in skeletal homeostasis and repair.

Optimal combination of arthroplasty type, fixation method, and postoperative rehabilitation protocol for complex proximal humerus fractures in the elderly: a network meta-analysis.

BACKGROUND: The purpose of this study was to define the optimal combination of surgical technique and postoperative rehabilitation protocol for elderly patients undergoing either hemiarthroplasty (HA) or reverse total shoulder arthroplasty (rTSA) for acute proximal humerus fracture (PHF) by performing a network meta-analysis of the comparative studies in the literature. METHODS: A systematic review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines of MEDLINE, EMBASE, and Cochrane Library was screened from 2007 to 2023. Inclusion criteria were level I-IV studies utilizing primary HA and/or rTSA published in a peer-reviewed journal, that specified whether humeral stems were cemented or noncemented, specified postoperative rehabilitation protocol, and reported results of HA and/or rTSA performed for PHF. Early range of motion (ROM) was defined as the initiation of active ROM at ≤3 weeks after surgery. Level of evidence was evaluated based on the criteria by the Oxford Centre for Evidence-Based Medicine. Clinical outcomes were compared using a frequentist approach to network meta-analysis with a random-effects model that was performed using the netmeta package version 0.9-6 in R. RESULTS: A total of 28 studies (1119 patients) were included with an average age of 74 ± 3.7 and mean follow-up of 32 ± 11.1 months. In the early ROM cohort (Early), the mean time to active ROM was 2.4 ± 0.76 weeks compared to 5.9 ± 1.04 weeks in the delayed ROM cohort (Delayed). Overall, rTSA-Pressfit-Early resulted in statistically superior outcomes including postoperative forward elevation (126 ± 27.5), abduction (116 ± 30.6), internal rotation (5.27 ± 0.74, corresponding to L3-L1), American Shoulder and Elbow Surgeons score (71.8 ± 17), tuberosity union (89%), and lowest tuberosity nonunion rate (9.6%) in patients ≥65 year old with acute PHF undergoing shoulder arthroplasty (all P ≤ .05). In total there were 277 (14.5%) complications across the cohorts, of which 89/277 (34%) were in the HA-Cement-Delayed cohort. HA-Cement-Delayed resulted in 2-times higher odds of experiencing a complication when compared to rTSA-Cement-Delayed (P = .005). Conversely, rTSA-Cement-Early cohort followed by rTSA-Pressfit-Early resulted in a total complication rate of 4.7% and 5.4% (odds ratios, 0.30; P = .01 & odds ratios, 0.42; P = .05), respectively. The total rate of scapular notching was higher in the cemented rTSA subgroups (16.5%) vs. (8.91%) in the press fit rTSA subgroups (P = .02). CONCLUSION: Our study demonstrates that patients ≥65 years of age, who sustain a 3-or 4-part PHF achieve the most benefit in terms of ROM, postoperative functional outcomes, tuberosity union, and overall complication rate when undergoing rTSA with a noncemented stem and early postoperative ROM when compared to the mainstream preference-rTSA-Cement-Delayed.

Does Flipping From Prone to Supine for Medial Malleolar Fixation of Trimalleolar Ankle Fractures Improve Results?

There has been a paradigm shift towards fixing the posterior malleolus in trimalleolar ankle fractures. This study evaluated whether a surgeon's preference to intraoperatively flip or not flip patients from prone to supine for medial malleolar fixation following repair of fibular and posterior malleoli impacted surgical outcomes. A retrospective patient cohort treated at a large urban academic center and level 1 trauma center was reviewed to identify all operative trimalleolar ankle fractures initially positioned prone. One hundred and forty-seven patients with mean 12-month follow-up were included and divided based on positioning for medial malleolar fixation, prone or supine (following closure, flip and re-prep, and drape). Data was collected on patient demographics, injury mechanism, perioperative variables, and complication rates. Postoperative reduction films were reviewed by orthopedic traumatologists to grade the accuracy of anatomic fracture reduction. Overall, 74 (50.3%) had the medial malleolus fixed prone, while 73 (49.7%) were flipped and fixed supine. No differences in demographics, injury details, and fracture type existed between the groups. The supine group had a higher rate of initial external fixation (p = .047), longer operative time in minutes (p < .001), and a higher use of plate and screw constructs for medial malleolar fixation (p = .019). There were no differences in clinical and radiographic outcomes and complication rates. This study demonstrated that intraoperative change in positioning for improved medial malleolar visualization in trimalleolar ankle fractures results in longer operative times but similar radiographic and clinical results. The decision of operative position should be based on surgeon comfort.

Surgical repair of large segmental bone loss with the induced membrane technique: patient reported outcomes are comparable to nonunions without bone loss.

OBJECTIVE: To compare the outcomes of patients with segmental bone loss who underwent repair with the induced membrane technique (IMT) with a matched cohort of nonunion fractures without bone loss. DESIGN: Retrospective analysis on prospectively collected data. SETTING: Academic medical center. PATIENTS: Two cohorts of patients, those with upper and lower extremity diaphyseal large segmental bone loss and those with ununited fractures, were enrolled prospectively between 2013 and 2020. Sixteen patients who underwent repair of 17 extremities with segmental diaphyseal or meta-diaphyseal bone defects treated with the induced membrane technique were identified, and matched with 17 patients who were treated for 17 fracture nonunions treated without an induced membrane. Sixteen of the bone defects treated with the induced membrane technique were due to acute bone loss, and the other was a chronic aseptic nonunion. MAIN OUTCOME MEASUREMENTS: Healing rate, time to union, functional outcome scores using the Short Musculoskeletal Functional Assessment (SMFA) and pain assessed by the Visual Analog Scale (VAS). RESULTS: The initial average defect size for patients treated with the induced membrane technique was 8.85 cm. Mean follow-up times were similar with 17.06 ± 10.13 months for patients treated with the IMT, and 20.35 ± 16.68. months for patients treated without the technique. Complete union was achieved in 15/17 (88.2%) of segmental bone loss cases treated with the IMT and 17/17 (100%) of cases repaired without the technique at the latest follow up visit. The average time to union for patients treated with the induced membrane technique was 13.0 ± 8.4 months and 9.64 ± 4.7 months for the matched cohort. There were no significant differences in reported outcomes measured by the SMFA or VAS. Patients treated with the induced membrane technique required more revision surgeries than those not treated with an induced membrane. CONCLUSION: Outcomes following treatment of acute bone loss from the diaphysis of long bones with the induced membrane technique produces clinical and radiographic outcomes similar to those of long bone fracture nonunions without bone loss that go on to heal. LEVEL OF EVIDENCE: III.

Non-psychoactive Cannabidiol Prevents Osteoporosis in an Animal Model and Increases Cell Viability, Proliferation, and Osteogenic Gene Expression in Human Skeletal Stem and Progenitor Cells.

Cannabidiol (CBD), the non-psychoactive component of the Cannabis sativa plant, is marketed as a potential therapeutic agent and has been studied for its roles in reducing inflammation and managing neuropathic pain. Some studies have reported that CB1 and CB2 receptor activation can attenuate and reverse bone loss in experimental animal models. Despite this, little is known about the impact of CBD on fracture healing. We investigated the effects of CBD in vitro using human osteoprogenitor cells and in vivo via murine femur fracture and osteoporosis models. In vitro mesenchymal stem cells were treated with increasing concentrations of crystalized pharmaceutical grade CBD or vehicle solution. Cell viability and proliferation were significantly increased in cells treated with CBD compared to vehicle control. Osteocalcin expression was also significantly higher in the CBD-treated human stem cells compared to vehicle control. In vivo the effect of CBD on bone mineral density and fracture healing in mice was examined using a two-phase experimental approach. Fluoxetine was used for pharmacologic induction of osteoporosis and surgical oophorectomy (OVX) was used for hormonal induction of osteoporosis. X-ray and microCT analysis showed that CBD prevented both fluoxetine- and OVX-induced osteoporosis. We found that while OVX resulted in delayed bone healing in control mice, CBD-pretreated mice exhibited normal bone healing. Collectively these in vitro and in vivo findings suggest that CBD exerts cell-specific effects which can be exploited to enhance bone metabolism. These findings also indicate that CBD usage in an osteoporotic population may positively impact bone morphology, warranting further research.

Biologics in Spine Fusion.

Achieving fusion in spine surgery can be challenging because of patient factors such as smoking and diabetes. The consequences of pseudarthrosis can be severe, including pain, instability, and additional surgery. Autologous iliac crest bone graft is the historical standard for augmenting spine fusion, providing high rates of fusion throughout the cervical, thoracic, and lumbar spine. Harvest of autologous iliac crest bone can be associated with comorbidities and this has led to development of alternative biologic materials to enhance spine fusion. Substitutes include various forms of allograft products including decellularized allograft; demineralized bone matrix; synthetic materials including bioactive glass; and autologous and allograft mesenchymal stem cells. Bone morphogenetic proteins can be efficacious for fusion but have significant risks and are not suitable for all spine procedures. There is a wide variety of utilization of biologics for spine fusion that are influenced by spinal region, surgeon preference, surgical training, health system formulary, and cost.

Rosiglitazone induces adipogenesis of both marrow and periosteum derived mesenchymal stem cells during endochondral fracture healing.

BACKGROUND: Type 2 diabetes mellitus (T2DM) afflicts about six percent of the global population, and these patients suffer from a two-fold increased fracture risk. Thiazolidinediones (TZDs), including rosiglitazone, are commonly used medications in T2DM because they have a low incidence of monotherapy failure. It is known that rosiglitazone is associated with secondary osteoporosis, further increasing the fracture risk in an already susceptible population. However, it is not yet understood how rosiglitazone impacts endochondral bone healing after fracture. The aim of this study is to elucidate how rosiglitazone treatment impacts endochondral fracture healing, and how rosiglitazone influences the differentiation of skeletal stem and progenitor cells from the bone marrow and the periosteum. METHODS: An in-vivo mouse femur fracture model was employed to evaluate differences in fracture healing between mice treated with and without rosiglitazone chow. Fracture healing was assessed with histology and micro computed tomography (µCT). In-vitro assays utilized isolated mouse bone marrow stromal cells and periosteal cells to investigate how rosiglitazone impacts the osteogenic capability and adipogenicity of these cells. RESULTS: The in-vivo mouse femur fracture model showed that fracture callus in mice treated with rosiglitazone had significantly more adipose content than those of control mice that did not receive rosiglitazone. In addition, µCT analysis showed that rosiglitazone treated mice had significantly greater bone volume, but overall greater porosity when compared to control mice. In-vitro experimentation showed significantly less osteogenesis and more adipogenesis in bone marrow derived progenitor cells that were cultured in osteogenic media. In addition, rosiglitazone treatment alone caused significant increases in adipogenesis in both bone marrow and periosteum derived cells. CONCLUSION: Rosiglitazone impairs endochondral fracture healing in mice by increasing adipogenesis and decreasing osteogenesis of both bone marrow and periosteum derived skeletal progenitor cells.

Transosseous tunnels versus suture anchors for the repair of acute quadriceps and patellar tendon ruptures: A systematic review and meta-analysis of biomechanical studies.

BACKGROUND: Multiple techniques have been developed for the repair of acute quadriceps and patellar tendon ruptures with the goal of optimizing clinical outcomes while minimizing complications and costs. The purpose of this study was to evaluate the biomechanical properties of transosseous tunnels and suture anchors for the repair of quadriceps and patellar tendon ruptures. METHODS: A systematic review of the PubMed and Embase databases was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using specific search terms and eligibility criteria. Meta-analysis was performed by fixed-effects models for studies of low heterogeneity (I2 <25%) and random-effects models for studies of moderate to high heterogeneity (I2 ≥25%). RESULTS: A total of 392 studies were identified from the initial literature search with 7 studies meeting the eligibility criteria for quadriceps tendon repair and 8 studies meeting the eligibility criteria for patellar tendon repair. Based on the random-effects model for total gap formation and load to failure for quadriceps tendon repair, the mean difference was 8.88 mm (95% CI, -8.31 mm to 26.06 mm; p = 0.31) in favor of a larger gap with transosseous tunnels and -117.25N (95%CI, -242.73N to 8.23N; p = 0.07) in favor of a larger load to failure with suture anchors. A similar analysis for patellar tendon repair demonstrated a mean difference of 2.86 mm (95% CI, 1.08 mm to 4.64 mm; p = 0.002) in favor of a larger gap with transosseous tunnels and -56.34N (95% CI, -226.75 to 114.07N; p = 0.52) in favor of a larger load to failure with suture anchor repair. CONCLUSIONS: Transosseous tunnels are biomechanically similar to suture anchors for quadriceps tendon repair. Patellar tendon repair may benefit from reduced gap formation after cycling with suture anchor repair, but the load to failure for both techniques is biomechanically similar. Additional studies are necessary to evaluate these and alternative repair techniques. LEVEL OF EVIDENCE: Systematic review and meta-analysis of biomechanical studies, Level V.

Bone Tissue Engineering Strategies for Alveolar Cleft: Review of Preclinical Results and Guidelines for Future Studies.

The current standard of care for an alveolar cleft defect is an autogenous bone graft, typically from the iliac crest. Given the limitations of alveolar bone graft surgery, such as limited supply, donor site morbidity, graft failure, and need for secondary surgery, there has been growing interest in regenerative medicine strategies to supplement and replace traditional alveolar bone grafts. Though there have been preliminary clinical studies investigating bone tissue engineering methods in human subjects, lack of consistent results as well as limitations in study design make it difficult to determine the efficacy of these interventions. As the field of bone tissue engineering is rapidly advancing, reconstructive surgeons should be aware of the preclinical studies informing these regenerative strategies. We review preclinical studies investigating bone tissue engineering strategies in large animal maxillary or mandibular defects and provide an overview of scaffolds, stem cells, and osteogenic agents applicable to tissue engineering of the alveolar cleft. An electronic search conducted in the PubMed database up to December 2021 resulted in 35 studies for inclusion in our review. Most studies showed increased bone growth with a tissue engineering construct compared to negative control. However, heterogeneity in the length of follow up, method of bone growth analysis, and inconsistent use of positive control groups make comparisons across studies difficult. Future studies should incorporate a pediatric study model specific to alveolar cleft with long-term follow up to fully characterize volumetric defect filling, cellular ingrowth, bone strength, tooth movement, and implant support.

The standardized exploration of the radial nerve during humeral shaft fixation reduces the incidence of iatrogenic palsy.

BACKGROUND: The purpose of this study is to determine if a standardized protocol for radial nerve handling during humeral shaft repair reduces the incidence of iatrogenic nerve palsy post operatively. METHODS: Seventy-three patients were identified who underwent acute or reconstructive humeral shaft repair with radial nerve exploration as part of the primary procedure for either humeral shaft fracture or nonunion. All patients exhibited intact radial nerve function pre-operatively. A retrospective chart review and analysis identified patients who developed a secondary radial nerve palsy post-operatively. In each case, the radial nerve was identified and mobilized for protection, regardless of whether the implant necessitated the extensile exposure. RESULTS: Fractures were classified according to AO/OTA guidelines and included 23 Type 12A, 11 Type 12B, and 3 Type 12C. Eight patients had periprosthetic fractures and 28 fractures could not be classified. All patients in the cohort were fixed with locking plates. Surgery was indicated for 36 patients with humeral nonunions and 37 patients with acute humeral shaft fractures. Of the 73 patients, 2 (2.7%) developed radial nerve palsy following surgery, one from the posterior approach and one from the anterolateral approach. Both patients exhibited complete recovery of radial nerve function by 6-month follow-up. No significant differences (p > 0.05) were found in any demographic or surgical details between those with and without radial nerve injury. CONCLUSIONS: Nerve exploration identification and protection leads to a low incidence of transient radial nerve palsy compared to the rate reported in the current literature (2.7% compared to 6-24%). Thus, radial nerve exploration and mobilization should be considered when approaching the humeral shaft for acute fracture and nonunion repairs. LEVEL OF EVIDENCE: Level III.

Screws Alone for Acute Lisfranc Injuries Fixed Without Arthrodesis: A Better "Value" Than Plating in the Short Term.

This study compares outcomes of patients with Lisfranc injuries treated with screw only fixation constructs to those treated with dorsal plate and screw constructs. Seventy patients who underwent surgical treatment for acute Lisfranc injury without arthrodesis and minimum 6-month (mean >1-year) follow-up were identified. Demographics, surgical information, and radiographic imaging were reviewed. Cost data were compared. The primary outcome measure was the American Orthopedic Foot and Ankle Surgery (AOFAS) midfoot score. Univariate analysis through independent sample t tests, Mann-Whitney U, and chi-squared compared the populations. Twenty-three (33%) patients were treated with plate constructs and 47 (67%) with screw only fixation. The plate group was older (49 ± 18 vs 40 ± 16 years, p = .029). More screw constructs treated isolated medial column injuries compared to plate constructs (92% vs 65%, p = .006). At latest follow-up (mean 14 ± 13 months), all tarsometatarsal joints were aligned. There was no difference in AOFAS midfoot scores. Plate patients experienced longer operations (131 ± 70 vs 75 ± 31 minutes, p < .001) and tourniquet time (101 ± 41 vs 69 ± 25 minutes, p = .001). Plate constructs were more expensive than screw ($2.3X ± $2.3X vs $X ± $0.4X, p < .001) ($X is the mean cost of screws alone). Plate patients had a higher incidence of wound complications (13% vs 0%, p = .012). Treatment of Lisfranc fracture dislocation injuries with screws only demonstrated a higher value procedure as similar outcomes were found amidst lower implant costs. Screw only fixation required a shorter operative and tourniquet time with less frequent wound complications. Screw only fixations proved mechanically sound enough to achieve goals of repair without inferior outcomes.

Approach variation affects outcomes after operative repair of lateral tibial plateau fractures.

PURPOSE: To determine if the type of approach used for treatment of lateral split-depression tibial plateau fractures affects clinical outcome and complications rate. METHODS: This is a retrospective review of 169 patients who presented between 01/2005 and 12/2020 to a Level-I trauma center for operative management of an isolated lateral Schatzker II tibial plateau fractures (AO/OTA Type 41B3.1) treated through a single anterolateral approach: a 90-degree "L" (L), longitudinal vertical (V), or "lazy S" (S). Postoperative radiographic, clinical, and functional outcomes were assessed at 3, 6, 12 months, and beyond. RESULTS: Average time to radiographic healing was longer in the S incision cohort (p < 0.05). Furthermore, patients within the S incision cohort developed more postoperative wound complications at follow-up when compared to those within the L and V incision cohorts (p < 0.05). Additionally, reoperation rates were greater in the S incision cohort (p < 0.05). Lastly, on physical examination of the knee, patients within the S incision cohort had significantly poorer knee range of motion (p < 0.05). CONCLUSIONS: Our study demonstrates that skin incision type in the anterolateral approach to the proximal tibia has an association with outcomes following operative repair of tibial plateau fractures. The information from this study can be used to inform surgeons about the potential complications and long-term outcomes that patients may experience when undergoing operative repair of a tibial plateau fracture through a specific incision type. LEVEL OF EVIDENCE: III.

Fixed-angle plate fixation and autogenous iliac crest graft for repair of distal metaphyseal femoral nonunion.

PURPOSE: To analyze clinical, radiographic and patient-reported outcomes of distal metaphyseal femoral nonunions treated with fixed-angle plates and screws. METHODS: All patients presenting with a distal metaphyseal femoral fracture nonunion repaired with fixed-angle plating from one urban level 1 trauma center and an orthopedic specialty hospital were identified. Baseline demographic, injury information, and outcomes (healing rates, Short Musculoskeletal Function Assessment, range of motion, and post-operative pain levels) at 12 months following nonunion repair were collected. Outcomes were evaluated between patients fixed with a blade plate and with a locking plate. RESULTS: Of these 31 patients, 27 (87.1%) healed after their index nonunion surgery, 2 (6.5%) healed after one reoperation, 1 (3.2%) healed after 2 reoperations, and 1 (3.2%) had a persistent nonunion but did not want further treatment. At one-year follow-up, the group demonstrated a significant improvement in functional recovery with a mean difference of 14.5 points (p = 0.007) when compared to status before fixed-angle fixation of the nonunion. There was also a significant change in patient-reported pain levels using the VAS scale with a mean difference of 2.0 points (p = 0.009). At one-year follow-up, 11 (39.3%) had full knee range of motion (0-130), 11 (39.3%) had flexion greater than 90 and less than 120°, and 6 (21.4%) had range of motion less than 90°. CONCLUSION: Patients who undergo fixed angle plating and autogenous bone grafting for distal femoral metapyseal nonunions demonstrate improved functional outcomes and VAS pain score at one year follow up.

Tibial plateau fractures in the elderly have clinical outcomes similar to those in younger patients.

BACKGROUND: The purpose of this study was to compare outcomes following surgical treatment of tibial plateau fractures in an elderly (≥ 65y) and non-elderly (< 65) population. METHODS: Patients with tibial plateau fractures were prospectively followed. Patients were included if they were operatively treated, had an Injury Severity Score of < 16, and had follow-up through 12 months. Clinical, radiographic, and functional outcomes were evaluated at the 3, 6, and 12-month follow-up points. RESULTS: Mean time to radiographic fracture union was by 4.68 and 5.26 months in young and elderly patients, respectively (p = 0.25). There was no difference in self-reported baseline SMFA (p = 0.617). SMFA scores were better in younger patients at 3 months (p = 0.031), however this did not hold when multivariate modeling controlled for other factors. There was no difference at 6 and 12 months (p = 0.475, 0.392). There was no difference in range of knee motion at 3 months. At 6 and 12 months, young patients had statistically but not clinically better range of knee motion (p = 0.045, 0.007). There were no differences in overall reoperation rates, conversion arthroplasty, post-traumatic osteoarthritis or wound complications. CONCLUSIONS: Age greater than 65 does not appear to portend poorer outcomes after surgical repair of a tibial plateau fracture. The complication profiles are similar. Elderly and younger patients had similar function at 12 months compared to their baseline. These data suggest that age should not be a disqualifying factor when considering whether a patient with a tibial plateau fracture should be treated operatively.

Home discharge location is safest following fracture of the hip.

PURPOSE: To determine the factors associated with discharge location in patients with hip fractures and whether home discharge was associated with a lower readmission and complication rate. METHODS: Hip fracture patients who presented to our academic medical center for operative management of a hip fracture were enrolled into an IRB-approved hip fracture database. Radiographs, demographics, and injury details were recorded at the time of presentation. Patients were grouped based upon discharge disposition: home (with or without home services), acute rehabilitation facility (ARF), or sub-acute rehabilitation facility (SAR). RESULTS: The cohorts differed in marital status, with a greater proportion of patients discharged to home being married (51.7% vs. 43.8% vs. 34.1%) (P < 0.05). Patients discharged to home were less likely to require an assistive device (P < 0.05). Patients discharged to home experienced fewer post-operative complications (P < 0.05) and had lower readmission rates (P < 0.05). Being married was associated with an increased likelihood of discharge to home (OR = 1.679, CI = 1.391-2.028, P < 0.001). Being enrolled in Medicare/Medicaid was associated with decreased odds of discharge to home (OR = 0.563, CI = 0.457-0.693, P < 0.001). Use of an assistive device was associated with decreased odds of discharge to home (OR = 0.398, CI = 0.326-0.468, P < 0.001). Increases in CCI (OR = 0.903, CI = 0.846-0.964, P = 0.002) and number of inpatient complications (OR = 0.708, CI = 0.532-0.943, P = 0.018) were associated with decreased odds of home discharge. CONCLUSION: Hip fracture patients discharged to home were healthier and more functional at baseline, and also less likely to have had a complicated hospital course. Those discharged to home also had lower rates of readmission and post-operative complications. LEVEL OF EVIDENCE: III.

Decreasing Postoperative Opioid Prescriptions After Orthopedic Trauma Surgery: The "Lopioid" Protocol.

OBJECTIVE: To assess the effectiveness of a multimodal analgesic regimen containing "safer" opioid and non-narcotic pain medications in decreasing opioid prescriptions after surgical fixation in orthopedic trauma. DESIGN: Retrospective cohort study. SETTING: One urban, academic medical center. SUBJECTS: Patients with traumatic fracture from 2018 (n=848) and 2019 (n=931). METHODS: In 2019, our orthopedic trauma division began a standardized protocol of postoperative pain medications that included 50 mg of tramadol four times daily, 15 mg of meloxicam once daily, 200 mg gabapentin twice daily, and 1 g of acetaminophen every 6 hours as needed. This multimodal regimen was dubbed the "Lopioid" protocol. We compared patients who received this protocol with all patients from the prior year who had followed a standard protocol that included Schedule II narcotics. RESULTS: Greater mean morphine milligram equivalents were prescribed at discharge from fracture surgery under the standard protocol than under the Lopioid protocol (252.3 vs 150.0; P < 0.001), and there was a difference in the type of opioid medication prescribed (P < 0.001). There was a difference in the number of refills filled for patients discharged with opioids after surgical treatment between the standard and Lopioid cohorts (0.31 vs 0.21; P = 0.002). There were no differences in the types of medication-related complications (P = 0.710) or the need for formal pain management consults (P = 0.199), but patients in the Lopioid cohort had lower pain scores at discharge (2.2 vs 2.7; P = 0.001). CONCLUSIONS: The Lopioid protocol was effective in decreasing the amount of Schedule II narcotics prescribed at discharge and the number of opioid refills after orthopedic surgery for fractures.

Age-related inflammation triggers skeletal stem/progenitor cell dysfunction.

Aging is associated with impaired tissue regeneration. Stem cell number and function have been identified as potential culprits. We first demonstrate a direct correlation between stem cell number and time to bone fracture union in a human patient cohort. We then devised an animal model recapitulating this age-associated decline in bone healing and identified increased cellular senescence caused by a systemic and local proinflammatory environment as the major contributor to the decline in skeletal stem/progenitor cell (SSPC) number and function. Decoupling age-associated systemic inflammation from chronological aging by using transgenic Nfkb1KO mice, we determined that the elevated inflammatory environment, and not chronological age, was responsible for the decrease in SSPC number and function. By using a pharmacological approach inhibiting NF-κB activation, we demonstrate a functional rejuvenation of aged SSPCs with decreased senescence, increased SSPC number, and increased osteogenic function. Unbiased, whole-genome RNA sequencing confirmed the reversal of the aging phenotype. Finally, in an ectopic model of bone healing, we demonstrate a functional restoration of regenerative potential in aged SSPCs. These data identify aging-associated inflammation as the cause of SSPC dysfunction and provide mechanistic insights into its reversal.

Iliac Crest and Distal Radius Autografts Exhibit Distinct Cell-Intrinsic Functional Differences.

PURPOSE: Autologous bone grafts demonstrate osteoconductive, osteoinductive, and osteogenic properties. Hand surgeons commonly augment surgical fixation with autografts to promote fracture healing. This study compared the intrinsic stem cell-like properties of 2 commonly used autograft sources in hand surgery: the iliac crest and distal radius. METHODS: A total of 9 subjects who received an iliac crest bone graft and distal radius bone graft harvest as a part of the standard care of distal radius malunion or nonunion correction or scaphoid nonunion open reduction and internal fixation were enrolled in the study. Cells were isolated by serial collagenase digestion and subjected to fibroblast colony-forming units, osteogenesis, and adipogenesis assays. The expression levels of genes involved in osteogenesis and adipogenesis were confirmed using quantitative polymerase chain reaction. RESULTS: The cells isolated from the iliac crest bone graft compared with those isolated from the distal radius bone graft demonstrated significantly higher mean fibroblast colony-forming unit efficiency; increased osteogenesis, as measured using alizarin red quantification; increased adipogenesis, as measured using oil red O quantification; and higher expression levels of genes involved in osteogenesis and adipogenesis under the respective differentiation conditions. CONCLUSIONS: The cells isolated from the iliac crest bone graft demonstrated a higher fibroblast colony-forming unit capacity and an increased capability to undergo both osteogenesis and adipogenesis. CLINICAL RELEVANCE: Limited evidence exists comparing the intrinsic stem cell-like properties of the iliac crest and distal radius despite the widespread use of each source in hand and wrist surgery. The information from this investigation may assist hand and wrist surgeons with the selection of a source of autograft.

Autogenous iliac crest bone grafting for tibial nonunions revisited: does approach matter?

BACKGROUND: Tibial nonunion remains a considerable burden for patients and the surgeons who treat them. In recent years, alternatives to autogenous grafts for the treatment of tibial nonunions have been sought. The purpose of this study was to evaluate the efficacy of autogenous iliac crest bone graft (ICBG) in the treatment of tibial shaft nonunions. MATERIAL AND METHODS: Sixty-nine patients were identified who underwent ICBG for repair of atrophic or oligotrophic tibial nonunion and had complete data with at least one year of follow-up (mean 27.9 months). Surgical treatments consisted of revision/supplemental fixation ± ICBG. Surgical approaches for graft placement were either posterolateral (PL), anterolateral (AL), or direct medial (DM). Healing status, time to union, postoperative pain, and functional outcomes were assessed. RESULTS: Bony union was achieved by 97.1% (67/69) of patients at a mean time of 7.8 ± 3.2 months postoperatively. There was no significant difference in mean time to union between the three surgical approach groups: (PL (44.9%) = 7.3 months, AL (20.3%) = 9.2 months, DM (34.8%) = 7.6 months; p = 0.22). Intraoperative cultures obtained at the time of nonunion surgery were positive in 27.5% of patients (19/69). Positive cultures were associated with need for secondary surgery as 8/19 patients (42.1%) with positive cultures required re-operation. Two out of four patients that developed iliac donor site hematomas/infections requiring washout had positive intraoperative cultures as well. There was no difference in final SMFA among the three surgical approach groups. CONCLUSIONS: Autogenous ICBG remains the gold standard in the management of persistent tibial nonunions regardless of surgical approach. There is a small risk for complication at the iliac crest donor site. Given the high union rate, autogenous iliac crest bone grafting for tibial nonunion remains the gold standard for this difficult condition. LEVEL OF EVIDENCE: Level III.