Longitudinal Analysis of Circulating Markers of Bone Turnover Across Multiple Decades in Osteoporotic Women.

PURPOSE: The objective of this study was to analyze changes in serum markers of bone turnover across multiple decades in osteoporotic women compared with nonosteoporotic controls, to determine their utility as potential predictors for osteoporosis. Early prediction of those at risk for osteoporosis can enable early intervention before the irreversible loss of critical bone mass. METHODS: Serum samples were obtained from 20 women given the diagnosis of osteoporosis after age 46 years and 20 age-matched women with normal bone mineral density from 4 time points in their life (ages 25-31, 32-38, 39-45, and 46-60 years). Serum levels of bone turnover markers (propeptide of type I collagen, parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin, C-terminal telopeptide of type I collagen, sclerostin, osteoprotegerin, osteopontin, and 25-OH vitamin D) were measured using commercially available arrays and kits. We used logistic regression to assess these individual serum markers as potential predictors of osteoporosis, and mixed-effects modeling to assess the change in bone turnover markers between osteoporotic and control groups over time, then performed fivefold cross-validation to assess the classification ability of the models. RESULTS: Markers of bone turnover, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, sclerostin, and osteocalcin were all independent predictors at multiple time points; osteopontin was an independent predictor in the 39- to 45-year age group. Receiver operating characteristic analyses demonstrated moderately strong classification ability at all time points. Sclerostin levels among groups diverged over time and were higher in the control group than the osteoporotic group, with significant differences observed at time points 3 and 4. CONCLUSIONS: Serum markers of bone turnover may be used to estimate the likelihood of osteoporosis development in individuals over time. Although prospective validation is necessary before recommending widespread clinical use, this information may be used to identify patients at risk for developing low bone mineral density long before traditional screening would ostensibly take place. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Union Rates and Reported Range of Motion Are Acceptable After Open Forearm Fractures in Military Combatants.

BACKGROUND: High-energy open forearm fractures are unique injuries frequently complicated by neurovascular and soft tissue injuries. Few studies have evaluated the factors associated with nonunion and loss of motion after these injuries, particularly in the setting of blast injuries. QUESTIONS/PURPOSES: (1) In military service members with high-energy open forearm fractures, what proportion achieved primary or secondary union? (2) What is the pronation-supination arc of motion as stratified by the presence or absence of heterotopic ossification (HO) and synostosis? (3) What are the risks of heterotopic ossification and synostosis? (4) What factors may be associated with forearm fracture nonunion? METHODS: A retrospective study of all open forearm fractures treated at a tertiary military referral center from January 2004 to December 2014 was performed. In all, 76 patients were identified and three were excluded, leaving 73 patients for inclusion. All 73 patients had serial radiographs to assess for HO and union. Only 64 patients had rotational range of motion (ROM) data. All patients returned to the operating room at least once after initial irrigation and débridement to ensure the soft tissue envelope was stable before definitive fixation. The indication for repeat irrigation and débridement was determined by clinical appearance. Patient demographics, fracture and soft tissue injury patterns, surgical treatments, neurovascular status at the time of injury, incidence of infection, heterotopic ossification (defined as the presence of heterotopic bone visible on serial radiographs), radioulnar synostosis, bony status after initial definitive treatment (union, nonunion, or amputation), and forearm rotation at final followup were retrospectively obtained from chart review by someone other than the operating surgeon. Seventy-six open forearm fractures in 76 patients were reviewed; 73 patients were examined for osseous union as three went on to early amputation, and 64 patients had forearm ROM data available for analysis. Union was determined by earliest radiology or orthopaedic staff official dictation stating the fracture was healed. Nonunion was defined as the clinical determination by the orthopaedist for a repeat procedure to achieve bony union. Secondary union was defined as union after reoperation to achieve bony union, and final union was defined as overall percentage of patients who were healed at final followup. Of the patients analyzed for union, 20 had less than 1 year of followup, and of these, none had nonunion. Of the patients analyzed for ROM, eight patients had less than 6 months of followup (range, 84-176 days). Of these, one patient had decreased ROM, none had a synostosis, and the remaining had > 140° of motion. RESULTS: Initial treatment resulted in primary union in 62 of 73 patients (85%); secondary union was achieved in eight of 11 patients (73%); and final union was achieved in 70 of 73 patients (96%). Although pronation-supination arc in patients without HO was 140° ± 35°, a limited pronation-supination arc was primarily associated with synostosis (arc: 40° ± 40°; mean difference from patients without HO: 103° [95% confidence interval {CI}, 77°-129°], p < 0.001); patients with HO but without synostosis had fewer limitations to ROM than those with synostosis (arc: 110° ± 80°, mean difference: 77° [35°-119°], p < 0.001). Heterotopic ossification developed in 40 of 73 patients (55%), including a radioulnar synostosis in 14 patients (19%). Bone loss at the fracture site (relative risk (RR) 6.2; 95% CI, 1.8-21) and healing complicated by infection (RR, 9.9; 95% CI, 4.9-20) were associated with the development of nonunion after initial treatment. Other potential factors such as smoking status, vascular injury, both-bone involvement, need for free flap coverage and blast mechanism were not associated. CONCLUSIONS: Despite a high-energy mechanism of injury and high rate of soft tissue defects, the ultimate probability of fracture union in our series was high with a low infection risk. Nonunions were associated with bone loss and deep infection. Functional motion was achieved in most patients despite increased burden of HO and synostosis compared with civilian populations. However, if synostosis did not develop, HO itself did not appear to interfere with functional ROM. Future investigations may provide improved decision-making tools for timing of fixation and prophylactic means against HO synostosis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Proximal Femur Hounsfield Units on CT Colonoscopy Correlate With Dual-energy X-ray Absorptiometry.

BACKGROUND: Quantifying bone mineral density (BMD) on CT using commercial software demonstrates good-to-excellent correlations with dual-energy x-ray absorptiometry (DEXA) results. However, previous techniques to measure Hounsfield units (HUs) within the proximal femur demonstrate less successful correlation with DEXA results. An effective method of measuring HUs of the proximal femur from CT colonoscopy might allow for opportunistic osteoporosis screening. QUESTIONS/PURPOSES: (1) Do proximal femur HU measurements from CT colonoscopy correlate with proximal femur DEXA results? (2) How effective is our single HU measurement technique in estimating the likelihood of overall low BMD? (3) Does the relationship between our comprehensive HU measurement and DEXA results change based on age, sex, or time between studies? METHODS: This retrospective study investigated the measurement of HU of the femur obtained on CT colonoscopy studies compared with DEXA results. Between 2010 and 2017, five centers performed 9085 CT colonoscopy studies; of those, 277 (3%) also had available DEXA results and were included in this study, whereas 8809 (97%) were excluded for inadequate CT imaging, lack of DEXA screening, or lack of proximal femur DEXA results. The median number of days between CT colonoscopy and DEXA scan was 595 days; no patient was excluded based on time between scans because bone remodeling is a long-term process and this allowed subgroup analysis based on time between scans. Two reviewers performed HU measurements at four points within the proximal femur on the CT colonoscopy imaging and intraclass correlation coefficients were used to evaluate interrater reliability. We used Pearson correlation coefficients to compare the comprehensive (average of eight measurements) and a single HU measurement with each DEXA result-proximal femur BMD, proximal femur T-score, femoral neck BMD, and femoral neck T-score-to identify the best measurement technique within this study. Based on their lowest DEXA T-score, we stratified patients to a diagnosis of osteoporosis, osteopenia, or normal BMD. We then calculated the area under the receiver operator characteristic curves (AUCs) to evaluate the classification ability of a single HU value to identify possible threshold(s) for detecting low BMD. For each subgroup analysis, we calculated Pearson correlation coefficients between DEXA and HUs and evaluated each subgroup's contribution to the overall predictive model using an interaction test in a linear regression model. RESULTS: The Pearson correlation coefficient between both the comprehensive and single HU measurements was highest compared with the proximal femur T-score at 0.75 (95% confidence interval [CI], 0.69-0.80) and 0.74 (95% CI, 0.68-0.79), respectively. Interobserver reliability, measured with intraclass correlation coefficients, for the comprehensive and single HU measurements was 0.97 (95% CI, 0.72-0.99) and 0.96 (95% CI, 0.89-0.98), respectively. Based on DEXA results, 20 patients were osteoporotic, 167 had osteopenia, and 90 patients had normal BMD. The mean comprehensive HU for patients with osteoporosis was 70 ± 30 HUs; for patients with osteopenia, it was 110 ± 36 HUs; and for patients with normal BMD, it was 158 ± 43 HUs (p < 0.001). The AUC of the single HU model was 0.82 (95% CI, 0.77-0.87). A threshold of 214 HUs is 100% sensitive and 59 HUs is 100% specific to identify low BMD; a threshold of 113 HUs provided 73% sensitivity and 76% specificity. When stratified by decade age groups, each decade age group demonstrated a positive correlation between the comprehensive HU and proximal femur T-score, ranging between 0.71 and 0.83 (95% CI, 0.59-0.91). Further subgroup analysis similarly demonstrated a positive correlation between the comprehensive HU and proximal femur T-score when stratified by > 6 months or < 6 months between CT and DEXA (0.75; 95% CI, 0.62-0.84) as well as when stratified by sex (0.70-0.76; 95% CI, 0.48-0.81). The linear regression model demonstrated that the overall positive correlation coefficient between HUs and the proximal femur T-score is not influenced by any subgroup. CONCLUSIONS: Our measurement technique provides a reproducible measurement of HUs within the proximal femur HUs on CT colonoscopy. Hounsfield units of the proximal femur based on this technique can predict low BMD. These CT scans are frequently performed before initial DEXA scans are done and therefore may lead to earlier recognition of low BMD. Future research is needed to validate these results in larger studies and to determine if these results can anticipate future fracture risk. LEVEL OF EVIDENCE: Level III, diagnostic study.

Fascia iliaca blockade with the addition of liposomal bupivacaine vs. plain bupivacaine for perioperative pain management following hip arthroscopy.

PURPOSE: A newer formulation of bupivacaine, encapsulated within carrier molecules, has garnered attention for its role in providing extended post-operative analgesia. The purpose was to evaluate the addition of liposomal bupivacaine to fascia iliaca blockade during hip arthroscopy. METHODS: Retrospective cohort study of patients undergoing hip arthroscopy with a pre-operative fascia iliaca blockade with either liposomal bupivacaine (Group 1; 266mg + 20 cc 0.5% plain bupivacaine) or bupivacaine (Group 2; 40 cc 0.25% plain bupivacaine). All patients received standardized pre-operative oral pain medications. The primary outcome was the defense veteran pain rating scale (DVPRS). Secondary outcomes included duration of hospital admission, PACU opioid use, PACU pain scores, and duration of nerve blockade. RESULTS: Thirty-eight males and 30 females, mean age of 33 years (range 14-56). There was no difference in pre-operative DVPRS between the groups (n.s.). There was no difference in post-operative DVPRS pain scores at POD0 (3.7 vs. 3.9, n.s.), POD1 (4.2 vs. 3.8, n.s.), POD2 (4.2 vs. 3.7, n.s.), POD3 (3.9 vs. 3.7, n.s.) or POD14 (2.2 vs. 2.4, n.s.). Group 1 trended towards longer mean total hospital admission time (872 vs. 822 min, n.s.), and greater mean morphine equivalents administered in the PACU (33 vs. 29 mg, n.s.). 68% of patients in group 1 reported continued anterior thigh numbness at POD3, compared to 34% in group 2 (p = 0.008). CONCLUSIONS: Despite the advertised benefits of prolonged post-operative analgesia using liposomal bupivacaine, there were no significant differences in post-operative pain scores or PACU opioid consumption. Our results support that acceptable pain scores are successfully achieved at all time periods with the use of multimodal analgesia including fascia iliaca blockade despite the type of pain medication administered. LEVEL OF EVIDENCE: III.

Frequency of Bone Health Presentations at National Hand Meetings.

PURPOSE: The purpose of this study was to determine the frequency with which osteoporosis topics (screening, medical treatment, and fracture prevention) are presented at national hand surgery meetings. This was compared with the frequency of the same topics presented at the Orthopaedic Trauma Association (OTA) annual meetings. METHODS: The annual meeting programs for the American Society for Surgery of the Hand (ASSH), the American Association for Hand Surgery (AAHS), and the OTA from the previous 10 years (2007-2016) were searched for presentations that covered bone health at each of these meetings. We categorized the presentations as either instructional or research. RESULTS: There were 2 bone health instructional presentations at hand surgery meetings in contrast to 13 presentations at OTA meetings over the last 10 years. For the last 9 years, the OTA has featured at least 1 instructional presentation on bone health every year. We identified 11 research presentations at the hand surgery meetings compared with 16 at the OTA meetings. CONCLUSIONS: Osteoporosis and bone health are infrequently presented instructional topics at national hand meetings compared with OTA meetings. The cause of the difference is unclear and likely multifactorial, varying each year with different program chairs and committees. The level of involvement of hand surgeons in osteoporosis management is controversial; however, incorporation of this topic may stimulate discussion and help identify solutions for this controversy. CLINICAL RELEVANCE: It may benefit hand surgeons to place more importance on osteoporosis screening and treatment. We believe that there should be an annual instructional course on this topic at the ASSH and AAHS meetings.

The Use of Distal Ulnar Hounsfield Units to Predict Future Fragility Fracture Risk.

PURPOSE: Distal ulnar Hounsfield unit (HU) measurements obtained from computed tomography (CT) scans of the wrist can be used to accurately screen for low bone mineral density. It is unknown whether HU measurements can also predict the risk of future fragility fractures. Therefore, the purpose of this study was to determine if the HU values of the distal ulna correlate to fragility fracture risk. METHODS: An electronic database of radiographs at a single institution was searched for all wrist CT scans, obtained for any reason, between January 1, 2002, and December 31, 2008, to allow a minimum of 5-year follow-up. Manual measurement of HU on sequential coronal CT slices of the distal ulnar head was taken, and mean values were recorded. Previously determined cutoff values for the diagnosis of low bone mineral density were implemented to stratify patients as at risk or not at risk for future fragility fracture. Medical records were then manually reviewed for the occurrence of any future fragility fracture (hip, spine, proximal humerus, or rib). RESULTS: There were 161 CTs in 157 patients and 34 fragility fractures in 21 patients, with a prevalence of 13.4%. The mean HU in the fragility fracture group was significantly lower (134.2 vs 197.1 HU). The percentage of low HU patients with fragility fractures was significantly higher (22.7% vs 3.8%). The odds ratio for fragility fracture in the low HU group was 7.4 (95% confidence interval, 2.1-26.2). Using previously determined cutoff values, the sensitivity and specificity of distal ulna HU values for identifying patients who would sustain at least 1 future fragility fracture were 85.7% and 55.2%, respectively. CONCLUSIONS: Patients with low distal ulnar HU were significantly more likely to sustain a subsequent fragility fracture. A determination of distal ulnar HUs represents a quick, simple tool to identify patients potentially at risk for fragility fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Glenoid neck Hounsfield units on computed tomography can accurately identify patients with low bone mineral density.

BACKGROUND: Osteoporosis is a costly and morbid disease with the first presentation often with a fragility fracture. The purpose of this study was to assess whether Hounsfield unit (HU) measurements on shoulder computed tomography could identify patients at risk of osteoporosis and aid in its diagnosis. METHODS: We identified patients who had both a computed tomography scan of the glenoid and a dual-energy x-ray absorptiometry scan. Dual-energy x-ray absorptiometry results and HU measurements of the patients' glenoid were recorded. Differences in HU measurements between patients with normal and abnormal central bone mineral density (BMD) were assessed. Correlations were calculated, and receiver operating characteristics were examined. RESULTS: A total of 51 glenoids met the criteria. The mean glenoid HU measurement was 140.6 (95% confidence interval [CI], 120.1-161.1) in the osteoporotic group, 168.1 (95% CI, 152.7-183.5) in the osteopenic group, and 233.2 (95% CI, 210.1-256.4) in the normal BMD group (P < .001). There was a significant correlation between mean glenoid HU measurement and patients' t scores in the femoral neck (r = 0.581), total hip (r = 0.524), and lumbar spine (r = 0.345). The area under the receiver operating characteristic curve was 0.918. With 197 HUs used as the cutoff for diagnosis of abnormal BMD, the positive predictive value was 96.6%. With 257.1 HUs used as the cutoff, the negative predictive value was 100%. CONCLUSION: A patient with an HU measurement below 197 has a 97% chance of having low BMD, and a patient with a measurement over 257 likely has normal BMD. In patients with measurements between these values, a definitive diagnosis should be aggressively pursued. Opportunistic screening for a modifiable disease that has significant morbidity and mortality rates at no additional cost, radiation, or time is of great value.

What Risk Factors Predict Recurrence of Heterotopic Ossification After Excision in Combat-related Amputations?

BACKGROUND: Heterotopic ossification (HO) is common after combat-related amputations and surgical excision remains the only definitive treatment for persistently symptomatic HO. There is no consensus in the literature regarding the timing of surgery, and recurrence frequency, reexcision, and complications have not been reported in large numbers of patients. QUESTIONS/PURPOSES: (1) What are the rates of symptomatic recurrence resulting in reexcision and other complications resulting in reoperation in patients with HO? (2) Is either radiographic or symptomatic recurrence dependent on timing and type of initial surgery, the experience of the surgeon in performing the procedure, the severity of preexcision HO, the presence of concomitant neurologic injury, or the use of postoperative HO prophylaxis? METHODS: Between March 2005 and March 2013 our institution treated 994 patients with 1377 combat-related major extremity amputations; of those, 172 amputations underwent subsequent excision of symptomatic HO. The mechanism of injury resulting in nearly all amputations (n = 168) was blast-related trauma. We reviewed medical records and radiographs to collect initial grade of HO, radiographic recurrence, complete compared with partial excision, concomitant neurologic injury, timing to initial surgery, surgeon experience, and use of postexcision prophylaxis with our primary study outcome being a return to the operating room (OR) for repeat excision of symptomatic HO. All 172 combat-related amputations were considered for this study irrespective of followup, which was noted to be robust, with 157 (91%) amputations having at least 6 months clinical followup by an orthopaedic surgeon or physiatrist (median, 20 months; range, 0-88 months). RESULTS: Eleven of 172 patients (6.5%) underwent reexcision of HO, and 67 complications resulting in return to the OR occurred in 53 patients (31%) of patients. Multivariate analysis of our primary outcome measure showed more frequent symptomatic recurrences requiring reexcision when initial excision was performed as a partial excision (p = 0.03; odds ratio [OR], 5.0; 95% confidence interval [CI], 1.2-29.6) or when the initial excision was performed within 180 days of injury (p = 0.047; OR, 4.1; 95% CI, 1.02-16.6). There was no association between symptomatic recurrence and HO grade, central nervous system injury, experience of the attending surgeon, or postoperative prophylaxis. Radiographic recurrence was observed when partial excisions (eight of 30 [27%]) were done compared with complete excisions (five of 77 [7%]; p = 0.008). CONCLUSIONS: HO is common after combat-related amputations, and patients undergoing surgical excision of HO for this indication often have complications that result in repeat surgical procedures. Partial excisions of immature lesions more often resulted in both symptomatic and radiographic recurrence. The likelihood of a patient undergoing reexcision can be minimized by performing a complete excision at least 180 days from injury to surgery with no evidence of a reduced risk of reexcision by waiting longer than 270 days. LEVEL OF EVIDENCE: Level III, therapeutic study.

Global Excision of Severe Heterotopic Ossification of the Shoulder: A Case Report.

CASE: A 21-year-old man sustained a closed glenohumeral fracture/dislocation as a pedestrian struck by a motor vehicle. He was treated nonoperatively and developed severe post-traumatic heterotopic ossification (HO) with near-complete shoulder ankylosis. We present our technique for safe surgical excision. CONCLUSIONS: Excision led to improvements in motion and quality of life at 1 year postoperatively. Recommendations for successful HO excision around the shoulder include excision after at least 180 days, appropriate preoperative imaging to include cross-sectional imaging and a 3D model, intraoperative fluoroscopy, well-serviced instruments, preparation for iatrogenic fracture and/or neurovascular injury, meticulous hemostasis, postoperative HO prophylaxis, immediate postoperative therapy, and involvement of a multidisciplinary team.

Effect of NSAIDs on Bone Healing Rates: A Meta-analysis.

INTRODUCTION: NSAIDs inhibit osteogenesis and may result in delayed union or nonunion. The purpose of this meta-analysis was to determine whether their use leads to delayed union or nonunion. METHODS: We systematically reviewed the literature reporting the effect of NSAIDs on bone healing. We included studies of pediatric and adult patients NSAID exposure and healing bone. The outcomes of interest were delayed union, nonunion, or pseudarthrosis with at least six months of follow-up. A maximum likelihood random-effects model was used to conduct meta-analysis and meta-regression. RESULTS: NSAID exposure increased delayed union or nonunion (odds ratio [OR], 2.07; confidence interval [CI], 1.19 to 3.61). No effect was noted in pediatrics (OR, 0.58; CI, 0.27 to 1.21) or low dose/short duration of exposure (OR, 1.68; CI, 0.63 to 4.46). CONCLUSION: Analysis of the literature indicates a negative effect of NSAIDs on bone healing. In pediatric patients, NSAIDs did not have a significant effect. The effect may be dose or time dependent because low-dose/short-duration exposure did not affect union rates.