Predictors of fracture healing in patients with recalcitrant nonunions treated with autologous culture expanded bone marrow-derived mesenchymal stromal cells.

The study reports the prospective outcome of treating severe recalcitrant fracture nonunion in patients with autologous bone marrow-derived mesenchymal stromal cells (BMSC) from 2003 to 2010 and analyze predictors of union. Autologous BMSC were culture expanded and inserted at nonunion site with or without carriers in addition to surgical stabilization of the fracture. Radiological union was ascertained by musculoskeletal radiologists on plain radiographs and/or CT scans. A logistic regression analysis was performed with cell-expansion parameters (cell numbers, cell doubling time) and known clinical factors (e.g., smoking and diabetes) as independent variables and fracture union as the dependent variable to identify the factors that influence bony healing. An Eq5D index score assessed the effect of treatment on general quality of health. A total of 35 patients (mean age 51+/-13 years) with established nonunion (median 2.9 years, 1-33) and, at least one failed nonunion surgery (median 4,1-14) received treatment. Fracture union was achieved in 21 patients (60%; 95%CI 44-75) at 2.6 years. Multiple penalized logistic regression revealed faster cell doubling time (p = 0.07), absence of diabetes (p = 0.003), less previous surgeries (p = 0.008), and lower age at cell implantation (p = 0.02) were significant predictors for fracture union. A significant increase in Eq5D index (p = 0.01) was noted with a mean rise of the score by 0.34 units (95%CI 0.11-0.58) at 1 year following the study. In summary, the study revealed cell doubling time as a novel in vitro parameter in conjunction with age, multiple surgeries, and diabetes as being significant predictors of the fracture union. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res 37:1303-1309, 2019.

Teriparatide treatment of femoral fracture nonunion that autogenous bone grafting failed to heal: a case report.

PURPOSE: Management of fracture nonunion is challenging as another surgical intervention for the patient is often a necessity, which has a huge impact on both quality of life and economic burden of the patient. Thus, a less aggressive and better accepted treatment for nonunion is required. METHODS: We gave teriparatide to a 45-year-old man with femoral fracture nonunion 1 year after he underwent surgery with autogenous bone grafting that failed to heal his initial nonunion. Successful union was obtained after once-daily administration of teriparatide for 9 months. RESULTS: Our case showed teriparatide could successfully treat a femoral fracture nonunion that autogenous bone grafting failed to heal. CONCLUSIONS: Teriparatide may provide an alternative treatment for fracture nonunion.

Debilitating Effects of Femoral Nonunion on Health-Related Quality of Life.

OBJECTIVE: The purpose of this study was to report the extent of the effects of femoral nonunion on health-related quality of life. DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS/PARTICIPANTS: One hundred eighty-seven consecutive patients (85 women, age 55.9 ± 16.9 years; 102 men, age 42.8 ± 16.1 years) with 188 nonunions of the femur, excluding those involving the hip or knee articular surfaces. INTERVENTION: Average nonunion duration was 28.5 months. 5.7% of the nonunions were infected, and the distal third was the most frequently involved segment. MAIN OUTCOME MEASUREMENTS: SF-12 Mental Component Summary (MCS) and Physical Component Summary (PCS) scores, Brief Pain Inventory (BPI), American Academy of Orthopaedic Surgeons Lower Limb Core Scale (LLCS), and Time Trade-Off (TTO) reported at the time of initial clinical evaluation at our center. RESULTS: The MCS scores averaged 43 ± 6.5, and the PCS scores averaged 26.3 ± 6.5, indicating the large adverse impact of femoral nonunion on mental and physical health, respectively. The BPI average intensity score averaged 5.1 ± 2.5, indicating moderate to severe pain. The LLCS averaged 53.9 ± 20.0, indicating substantial lower extremity-specific disability. The TTO questionnaire responses indicated that these patients were willing to trade an average of 38.3% of their remaining years of life to regain health. CONCLUSIONS: The impact of femoral shaft nonunion on physical health was comparable to end-stage hip arthrosis and tibial nonunion and worse than many other medical conditions. Femoral shaft nonunion is a debilitating chronic medical condition with substantial negative effects on health. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Negligence claims following non-union and malunion of long bone fractures: An analysis of 15 years of data.

INTRODUCTION: Non-unions and malunions are recognised to be complications of the treatment of long bone fractures. No previous work has looked at the implications of these complications from a medicolegal perspective. METHODS: A complete database of litigation claims in Trauma and Orthopaedic Surgery was obtained from the NHS Litigation Authority. Two separate modalities of the treatment of long bone fractures were examined i) non-union and ii) acquired deformity. The type of complaint, whether defended or not, and costs were analysed. RESULTS: There were claims of which 97 related to non-union and 32 related to postoperative limb deformity. The total cost was £8.2 million over a 15-year period in England and Wales. Femoral and tibial non-unions were more expensive particularly if they resulted in amputation. Rotational deformity cost nearly twice as much as angulation deformities. CONCLUSIONS: The cosmetic appearances of rotational malalignment and amputation results in higher compensation; this reinforces an outward perception of outcome as being more important than harmful effects. Notwithstanding the limitations of this database, there are clinical lessons to be gained from these litigation claims.

Operative Versus Nonoperative Treatment of Displaced Intra-Articular Calcaneal Fractures: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To compare the clinical outcomes of operative and nonoperative treatment for displaced intra-articular calcaneal fractures (DIACFs). DATA SOURCES: PubMed, Embase, Cochrane library, and ClinicalTrial.gov. STUDY SELECTION: Randomized controlled trials comparing operative and nonoperative treatment for DIACFs. DATA EXTRACTION: Information on study methods and clinical outcomes. DATA SYNTHESIS: We performed data synthesis on relevant clinical outcomes. Weighted mean differences with 95% confidence intervals were calculated for continuous data and relative risks with 95% confidence intervals were calculated for dichotomous data. A fixed-effect model or a random-effect model was used. RESULTS: Seven randomized controlled trials involving 908 patients were included. Operative treatment for DIACFs reduced problems associated with shoe wear and increased walking ability but increased the risks of overall complications and infection. There were no significant differences between the groups in American Orthopaedic Foot and Ankle Society scores, The Short Form (36) Health Survey, return to work, rate of subsequent subtalar fusion, or the rate of reflex sympathetic dystrophy. CONCLUSIONS: This meta-analysis documented that when surgery was performed correctly, better shoe wear and improved walking ability could be expected. These outcomes seemed to be based on the surgeon's ability to obtain an acceptable reduction. Benefits were tempered by the increase in wound complications associated with this intervention. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Time Trade-Off as a Measure of Health-Related Quality of Life: Long Bone Nonunions Have a Devastating Impact.

BACKGROUND: Long bone nonunions have an important impact on a patient's quality of life. The purpose of this study was to compare long bone nonunions with use of the Time Trade-Off direct measure to compute utility scores and to determine which nonunion anatomic location had the lowest health-related quality of life. The Time Trade-Off assesses the percentage of a patient's remaining life that the patient would be willing to trade for perfect health. METHODS: Eight hundred and thirty-two consecutive long bone nonunions with Time Trade-Off data were identified and were retrospectively studied from a prospectively collected patient database. Nonunions with infections and those involving the articular portion of the bone were recorded. Time Trade-Off utility scores were obtained for all nonunion cases upon their initial clinical evaluation by a single surgeon specializing in reconstructive trauma. RESULTS: The mean utility score of our nonunion cohort was 0.68 and it differed significantly by long bone (p = 0.037). Nonunions of the forearm had the lowest utility score (0.54), followed by the clavicle (0.59), femur (0.68), tibia or fibula (0.68), and humerus (0.71). Post hoc tests showed that patients with nonunions of the forearm had significantly lower utility scores (p = 0.031) compared with all other bones. CONCLUSIONS: Patients diagnosed with a long bone nonunion have a very low health-related quality of life. We found that this single cohort's mean utility score was 0.68. This result is well below that of illnesses such as type-I diabetes mellitus (0.88), stroke (0.81), and acquired immunodeficiency syndrome (0.79). We found that patients with forearm nonunions had the lowest utility scores. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The devastating effects of tibial nonunion on health-related quality of life.

BACKGROUND: Tibial nonunion is disabling, but to our knowledge no quantitative evaluation of its effect on health-related quality of life has been reported. METHODS: We evaluated 243 tibial shaft fracture nonunions in 237 consecutive patients (seventy-nine female [age, 49.4 ± 14.9 years] and 158 male [age, 46.3 ± 15.4 years]) who were referred to a single surgeon at our tertiary care center over a ten-year period. The most frequently affected tibial segment was the distal third (49%), and infection was present in 18% of all cases. RESULTS: The Short Form (SF)-12 Physical Component Summary score averaged 27.4 ± 6.7, indicating an extremely disabling effect on physical health. The AAOS (American Academy or Orthopaedic Surgeons) Lower Limb Core Scale score averaged 52.0 ± 19.4, also consistent with high levels of physical disability attributable to the lower limb. The SF-12 Mental Component Summary score averaged 42.3 ± 7.1, indicating a substantial detrimental effect on mental health. CONCLUSIONS: The impact of tibial shaft fracture nonunion on physical health was comparable with the reported impact of end-stage hip arthrosis and worse than that of congestive heart failure. Tibial shaft fracture nonunion is a devastating chronic medical condition that negatively affects both physical and mental health and quality of life.

Undisplaced femoral neck fractures--no problems? A consecutive study of 224 patients treated with internal fixation.

224 patients with undisplaced femoral neck fractures treated with two parallel Hansson hook pins were studied. After a mean follow-up time of 32 months (S.D. 5.2), 15% had a reoperation. 11% were considered failures, mostly avascular necrosis, and 9% had a secondary arthroplasty. Possible risk factors for poor outcome were analysed. Neither high age nor surgical delay was associated with increased failure rate. Survivors received a questionnaire, and 40% stated that they had mild or severe pain in the hip when walking, 25% had pain at rest and 25 stated that they thought "always" or "often" about their injury. The younger the patient, the more frequent the report of subjective pain. 51% of individuals under 80 years reported pain when walking, compared to 27% aged 80 or older (p=0.016). Corresponding numbers for pain at rest were 32 and 12% (p=0.034). The failure rate did not differ between the age groups, but the younger patients had more reoperations (p=0.046) and thought more frequently about their injury (p=0.016). An undisplaced femoral neck fracture is a major injury with a long-term daily discomfort in about 25% and clinical failure in 11%.

The infected nonunion of the tibia.

Ununited fracture of the tibia complicated by infection is not only a complex surgical problem but also a chronic and at times debilitating condition. The principle methods used to diagnose and stage posttraumatic tibial osteomyelitis are described. Infected nonunions of the tibia are characterized by the extent of bony loss and the presence of a functional ipsilateral fibula. Using this tibial staging criteria, a series of 37 infected nonunions of the tibia are reviewed. Twenty patients were male and 16 were female, with an average age of 33 years. The distal third of the tibia was involved in 19 patients, the middle third in 11, and proximal third in 7. Twenty three of the tibia were infected with > 1 organism. Thirty were Type 3 (tibial defect of 6 cm or less with a long and usable fibula), 4 Type 4 (tibial defect > 6 cm without usable fibula), and 3 Type 5 (tibial defect > 6 cm without usable fibula). The patients were evaluated at an average of 61 months after treatment. Union and eradication of infection were achieved in 35 of 37 patients. The results of the Health Impact Analysis suggest that the infected nonunion of the tibia represented a chronic and debilitating disorder with a lasting impact.

Quality of life assessment of patients with posttraumatic fracture nonunion, chronic refractory osteomyelitis, and lower-extremity amputation.

One hundred nine patients with long-bone fracture nonunion, chronic refractory osteomyelitis, and posttraumatic amputation were evaluated to assess the impact of chronic disability on the quality of life. The quality of life parameters were defined by a functional assessment instrument, the Arthritis Impact Measurement Scale (AIMS), and a Psychosocial Adjustment to Illness Scale (PAIS). A spouse PAIS self-report instrument was administered to assess the psychosocial adjustment of spouses or significant others. A final questionnaire was developed to determine the reasons, in order of their importance, for either continuing medical therapy or accepting amputation. The PAIS scores differed significantly between osteomyelitis patients and nonunion or amputation patients. The presence or absence of pain produced significant differences in AIMS and PAIS scores of nonunion and osteomyelitis patients. Subscale analysis of AIMS scores showed significant differences among the three groups with respect to health perception and scale of orthopaedic problem. The osteomyelitis patients were more severely affected than the nonunion or amputation patients. The PAIS was unable to detect any statistically significant differences in psychosocial adjustment of the spouses of patients in each of the three population groups. The most frequent reason for continuing medical and surgical management of nonunion and osteomyelitis was hopeful expectation for cure. The group who chose amputation did so in an attempt to put an end to the need for medical and surgical treatment. Differences in psychosocial and functional ability were related to disease diagnosis, pain, status of fracture healing, and timing of amputation. This study provides further insight into the quality of life experience for patients with long-term orthopaedic problems.

Psychosocial, functional, and quality of life assessment of patients with posttraumatic fracture nonunion, chronic refractory osteomyelitis, and lower extremity amputation.

One hundred nine patients with long-bone fracture nonunion, chronic refractory osteomyelitis, or posttraumatic amputation were evaluated for the impact of chronic disability on quality of life, as measured by the Arthritis Impact Measurement Scale (AIMS) and the Psychosocial Adjustment to Illness Scale (PAIS). A self-administered PAIS for spouses assessed psychosocial adjustment of spouses or significant others. A final questionnaire ranked the reasons for either continuing medical therapy or accepting amputation. The PAIS scores differed significantly between osteomyelitis patients and both nonunion and amputation patients (p less than .05). The presence or absence of pain produced significant differences in AIMS and PAIS scores of nonunion and osteomyelitis patients (p less than .05). Subscale analysis of AIMS scores revealed significant differences among the three groups in health perception and scale of orthopedic problem: osteomyelitis patients were more severely affected than nonunion or amputation patients. The PAIS detected no statistically significant difference in psychosocial adjustment of spouses of patients in the three population groups. The most common reason for continuing medical and surgical management of nonunion and osteomyelitis was expectation for cure. The amputee group chose ablation to avoid further treatment. Differences in psychosocial and functional ability were related to disease diagnosis, pain, status of fracture healing, and timing of amputation.

Failure of treatment of ununited fractures of the carpal scaphoid. The role of non-compliance.

We studied the results in thirty patients who had grafting of an ununited fracture of the carpal scaphoid bone. Psychiatric evaluations revealed that the thirteen patients who had a non-union of the initial scaphoid bone graft had significant psychiatric problems, whereas the seventeen patients in whom the non-union had healed after initial bone-grafting of the scaphoid did not have psychiatric abnormalities. Technically successful surgical revisions in the first group of patients did not result in significant clinical improvement. We concluded that most failures of the bone grafts were related to non-compliance on the part of the patient and that some of the operations could have been avoided if the underlying psychiatric problems had been recognized preoperatively.