A Case–Control Study of Quality of Life and Functional Impairment in Women with Long–Standing Vertebral Osteoporotic Fracture

There have been several studies of the impact of vertebral osteoporotic fracture on the quality of life and functionality of individual subjects. To date, however, no direct comparisons with age-matched normal subjects without vertebral fracture have been made. The radiographs of 145 female clinic patients with vertebral fractures were reviewed by the study physicians. The controls were recruited from the electoral role and by media appeal. One hundred and sixty-seven women had radiographs taken to determine those without vertebral fracture. Fracture subjects and controls had to be ambulant and were excluded if they had significant radiologic evidence of degenerative disk or joint disease of the spine. One hundred cases and one hundred controls were matched by 5-year age groups. The number, position and severity of the vertebral fracture on the lateral radiographs of the cases was recorded. Quality of life was measured using the Short Form-36 (SF-36) (maximum score 100) and a utility score calculated from thesese results (maximum score 1). Two measurements of functionality were employed: the Modified Barthel Index (MBI) to assess the activities of daily living (maximum score 100) and the Timed ‘Up & Go’ (TUG) that measured the time taken for the subject to rise from sitting in a chair, walk 3 m along a line, return to the chair and sit down. The fracture subjects had 2.9 + 1.6 (mean + SD) vertebral fractures and the time since last fracture was 5.1 + 4.8 years. The SF-36 physical function component summary index results were: fracture subjects 36 + 11, controls 48 + 9 (p < 0.001). The SF-36 mental health component summary index results were: fracture subjects 50 + 11, controls 54 + 8 (p <0.05). The utility scores were: fracture subjects 0.64 + 0.08, controls 0.72 + 0.07 (p <0.001). The MBI results were: fracture subjects 97 + 5, controls 99 + 1 (p< 0.01). The TUG results were: fracture subjects 13.8 + 7.3 s, controls 10.1 + 4.1 s (p <0.01). TUG and MBI scores correlated well with SF-36 scores; however, no domain of the SF-36 or functional measure correlated with either the number of vertebral fractures or the time since last vertebral fracture. Thus, clinically reported vertebral fractures impair both the quality of life and functionality of these subjects. The adverse impact of vertebral fracture on quality of life and functionality needs to be recognized by medical practitioners, subjects and the community, so that adequate health resources can be devoted to the prevention and treatment of this debilitating condition condition. Received: 17 June 1998 / Accepted: 28 October 1998     

Evaluation of the Potential Use of Trabecular Bone Score to Complement Bone Mineral Density in the Diagnosis of Osteoporosis: A Preliminary Spine BMD–Matched,Case-Control Study

The trabecular bone score (TBS) is a new parameter that is determined from gray-level analysis of dual-energy X-ray absorptiometry (DXA) images. It relies on the mean thickness and volume fraction of trabecular bone microarchitecture. This was a preliminary case-control study to evaluate the potential diagnostic value of TBS as a complement to bone mineral density (BMD), by comparing postmenopausal women with and without fractures. The sample consisted of 45 women with osteoporotic fractures (5 hip fractures, 20 vertebral fractures, and 20 other types of fracture) and 155 women without a fracture. Stratification was performed, taking into account each type of fracture (except hip), and women with and without fractures were matched for age and spine BMD. BMD and TBS were measured at the total spine. TBS measured at the total spine revealed a significant difference between the fracture and age– and spine BMD–matched nonfracture group, when considering all types of fractures and vertebral fractures. In these cases, the diagnostic value of the combination of BMD and TBS likely will be higher compared with that of BMD alone. TBS, as evaluated from standard DXA scans directly, potentially complements BMD in the detection of osteoporotic fractures. Prospective studies are necessary to fully evaluate the potential role of TBS as a complementary risk factor for fracture.     

Hip Fracture Risk and Cadmium in Erythrocytes: A Nested Case–Control Study with Prospectively Collected Samples

Several studies have investigated the relation between bone mass density and cadmium exposure, but only few studies have been performed on fractures and biomarkers of cadmium. This study analyzed the association between hip fracture risk and cadmium in erythrocytes (Ery-Cd). Prospective samples from the Northern Sweden Health and Disease Study’s biobank were used for 109 individuals who later in life had sustained a low-trauma hip fracture, matched with two controls of the same age and gender. The mean concentration of Ery-Cd (±SD) in case samples was 1.3 ± 1.4 versus 0.9 ± 1.0 μg/L in controls. The odds ratio (OR) was 1.63 [95 % confidence interval (CI) 1.10–2.42] for suffering a hip fracture for each microgram per liter increase in Ery-Cd. However, when taking smoking into consideration (never, former, or current), neither Ery-Cd nor smoking showed a statistically significant increase in fracture risk. Using multiple conditional logistic regression with BMI, height, and smoking, the estimated OR for a 1-μg/L increase in Ery-Cd was 1.52 (95 % CI 0.77–2.97). Subgroup analysis showed an increased fracture risk among women (OR = 1.94, 95 % CI 1.18–3.20, for a 1 μg/L increase), which also remained in the multiple analysis (OR = 3.33, 95 % CI 1.29–8.56). This study shows that fracture risk is associated with Ery-Cd. It is, however, not possible to draw firm conclusions on whether cadmium is the causal factor or whether other smoking-related factors cause this association. Subgroup analysis shows that cadmium is a risk factor for hip fracture among women.     

Knee Arthroplasty and Risk of Hip Fracture: A Population-Based,Case–Control Study

The majority of knee arthroplasties (KAs) are performed in patients with osteoarthritis (OA). Although bone mass may be increased in these patients, subjects with knee OA may have an increased risk of hip fracture, possibly due to an increased severity of falls. However, in patients with KAs, risk of hip fracture has not been studied extensively. We evaluated the association between KAs and hip fracture risk in a population-based case–control study using the Dutch PHARMO Record Linkage System (1991–2002, n = 33,104). Cases were patients with a first admission for hip fracture; controls were matched by age, gender, and geographic location. Neither group had a previous history of fracture. Time since first KA was calculated. Analyses were adjusted for disease and drug history. A 54% increased hip fracture risk was found in patients who underwent KA (adjusted [adj.] OR = 1.54, 95% CI 1.19–2.00). We found a strong effect modification by age in these patients: the youngest patients (aged 18–70 years) were at more increased risk for hip fracture (adj. OR = 2.76, 95% CI 1.16–6.59), while we could not detect a statistical increase in patients aged >80 years. Furthermore, the association tended to be greater during the first few years after surgery, although it did not reach statistical significance. We found that KAs are associated with a 54% increased risk of hip fracture, in particular among adult patients aged <71 years old. Fracture risk assessment could be considered in patients who are about to undergo a KA.     

Measurement of Trabecular Bone Score of the Spine by Low-Dose Imaging System (EOS®): A Feasibility Study

Purpose/Introduction: Measurement of trabecular bone score (TBS^®) of the lumbar spine on dual energy X-ray absorptiometry (DXA) devices improves fracture risk prediction. We conducted a proof of concept study to assess the feasibility of TBS^® measured on the low-dose imaging system EOS^®. Methods: TBS was assessed on both DXA and EOS^® in 122 patients aged ≥ 50 yr, receiving no anti-osteoporotic treatment. The TBS^® was computed on full-body EOS^® images, focusing on the lumbar spine region. The patients were also scanned with a DXA bone densitometer (Hologic) and the spine and hip bone mineral density (g/cm²) were computed. Results: TBS^® measurement on EOS^® was not possible in 34 patients due to technical problems. It could be measured on both DXA and EOS^® in 88 patients (28 with severe low-trauma fracture and 60 without fracture). TBS-EOS values were significantly lower in fractured patients compared to nonfractured patients. TBS-EOS was associated with the presence of fractures as reported by an AUC of 0.70. Odds ratio of TBS-EOS for the presence of severe low-trauma fracture was 2.00 [1.24–3.25], p?=?0.005. Conclusions: This proof of concept study, based on a prototype version of the TBS-EOS, demonstrated the feasibility of the measurement of TBS^® on low-dose EOS^® imaging devices. Results show that the TBS-EOS was lower in patients with severe low-trauma fractures compared to nonfractured patients independently from bone mineral density. Some technical issues need to be solved before its eventual use in routine clinical settings. Additional prospective studies are still needed to define the actual contribution of this new technique.     

Impaired Bone Health in Inflammatory Bowel Disease: A Case–Control Study in 80 Pediatric Patients

Previous studies have indicated that children with inflammatory bowel disease (IBD) may not achieve optimal bone mass. We evaluated the skeletal characteristics in children and adolescents with IBD. This cross-sectional cohort study comprised 80 IBD patients (median age 14.9?years, range 5-20) with a median disease duration of 3.4?years; 51 had ulcerative colitis, 26 Crohn disease, and 3 unspecified colitis. Eighty age- and gender-matched healthy subjects served as controls. Areal bone mineral density (aBMD), body composition, and vertebral fractures (VFs) were assessed by DXA. Bone age (BA) was determined for IBD patients. Findings were correlated with disease- and treatment-related parameters and biochemistry. IBD patients had lower BA-adjusted lumbar spine and whole-body aBMD (p?150?mg/kg for the preceding 3?years increased the risk for low whole-body aBMD (OR?=?5.5, 95?% CI 1.3-23.3, p?=?0.02). VFs were found in 11?% of patients and in 3?% of controls (p?=?0.02). IBD in childhood was associated with low aBMD and reduced bone mass accrual relative to muscle mass; the risk for subclinical VFs may be increased. These observations warrant careful follow-up and active preventive measures.     

Increased Bone Mineral Density and Decreased Prevalence of Osteoporosis in Cervical Ossification of the Posterior Longitudinal Ligament: A Case–Control Study

Bone and mineral metabolism has been reported to affect the development of the ossification of the posterior longitudinal ligament (OPLL). The aim of this study was to compare bone mineral densities (BMD) and rate of osteoporosis between cervical OPLL and a matched control group. We also investigated the correlation of BMD with the number of cervical spine levels involved with OPLL. From 1999 to August 2011, 178 patients with cervical OPLL underwent dual-energy X-ray absorptiometry (DXA) at our institute. The control group was age-, sex-, and body mass index (BMI)–matched with the OPLL group on a 1:1 basis. BMD was measured at the lumbar spine (L1–L4), femoral neck, and total femur using DXA. Age, sex, and BMI were the same in the OPLL and control groups. BMDs of the OPLL and control groups were significantly different in the lumbar spine, femoral neck, and total femur (p = 0.0001, 0.0001, 0.009, respectively). Rates of osteopenia and osteoporosis were lower in the OPLL than in the control group according to lumbar spine and femoral neck DXA (p = 0.01, 0.03, respectively). A positive correlation was observed between lumbar spine BMD and the number of cervical spine levels involved with OPLL (p = 0.004).     

Adenosquamous Carcinoma of the Head and Neck: A Case–Control Study with Conventional Squamous Cell Carcinoma

Adenosquamous carcinoma (AdSC) is considered a rare variant of squamous cell carcinoma (SCC) which is considered to be more clinically aggressive. Data is very limited with very little case matched data on outcomes in the literature. It is also unknown whether the quantity of the adenocarcinoma component affects outcomes. A retrospective case–control study with 23 cases of AdSC and 1137 SCC controls was conducted. Cases were matched by anatomic subsite, treatment, and, for oropharynx, by p16 status. The following variables were adjusted for in the analysis: T classification (T1/T2 vs. T3/T4), N classification (N0–N2a vs. N2b–N3), age, and smoking. The adenocarcinoma component was quantified by the number of high power fields containing glands as low, moderate, or high. AdSCs had a significantly greater risk of disease recurrence but largely, the differences were not statistically significant. The quantity of adenocarcinoma did not correlate with disease recurrence or survival. This case–control study on AdSC shows modestly more clinically aggressive behavior than conventional SCC, even while controlling for p16 status for oropharyngeal cases. Further, it suggests the current definition of AdSC, with no minimum requirement for gland formation, is clinically accurate.     

Factors Associated with Premalignant Epithelial Changes in Chronic Calculous Cholecystitis: A Case–Control Study

Introduction

Gallstones are known to be associated with premalignant changes in the gallbladder epithelium that range from atypical hyperplasia, metaplasia, dysplasia to carcinoma. Recognition of factors associated with these changes in patients with gallstones can potentially be helpful in identifying patients to whom prophylactic cholecystectomy can be offered to reduce the chances of developing carcinoma.

Objective

To identify factors associated with premalignant epithelial changes including atypical hyperplasia, metaplasia, and dysplasia in gallbladder mucosa in patients with chronic calculus cholecystitis.

Materials and methods

This was retrospective case–control study conducted over a period of 10 years from 2004 to 2014. Cases were patients with reported histopathological premalignant epithelial changes along with chronic calculus cholecystitis, and controls were patients without premalignant epithelial changes but chronic calculus cholecystitis. Controls were twice the number of the cases.

Results

Over study period, 92 patients were reported to have premalignant epithelial changes on gall bladder histopathology for whom 184 controls were selected. Of cases, 61 (66%) patients had atypical hyperplasia, while metaplasia and dysplasia were present in 26 (28%) and 5 (5%) cases, respectively. Mean age was 47.5 ± 14.5 years, and 74% of the study population were female. Wall thickness of more than 3 mm (OR = 4.14, p value < 0.001) turned out to be statistically significant independent variables associated with premalignant lesions in gallbladder mucosa.

Conclusion

Odds of premalignant epithelial change in gall bladder mucosa in patients with gall bladder wall thickness of more than 3 mm is four times the odds of patients with wall thickness less than 3 mm, and the effect is statistically significant. Prophylactic cholecystectomy should be considered for this group of patients.

     

Osteoporotic Vertebral Fracture Prevalence in Elderly Chinese Men and Women: A Comparison of Endplate/Cortex Fracture–Based and Morphometrical Deformity–Based Methods

This study aims to evaluate endplate/cortex fracture (ECF)-based method for detecting osteoporotic vertebral fracture (VF) in elderly Chinese population (age ≥ 65 years). The radiographs of 1954 elderly Chinese men (mean: 72.3 years) and 1953 elderly Chinese women (mean: 72.5 years) were evaluated according to Genant's morphometrical vertebral deformity (VD) severity criteria, as well as identified VF according to ECF without necessary requirement of VD. According to ECF, grade-1, -2, and -3 VF prevalence was 1.89%, 1.74%, and 2.25% in men, and 3.33%, 3.07%, and 5.89% in women, respectively. In men and women, 15.7% (35 of 223) and 34.5% (48 of 139) of vertebrae with VD grade-1 deformity were ECF(+, with fracture), respectively. In men and women, 89.7% (35 of 39) and 66.7% (48 of 72) of vertebrae with ECF grade-1 fracture had VD grade-1 deformity. For grade-1 change, ECF(+) subjects tended to have a lower BMD than the VD(+) subjects. In subjects with VD grade-2 deformity, those who were also EC (+) tended to have a lower BMD than those were ECF(?). In all grades, VD(?) and ECF(?) subjects tended to have highest BMD, whereas VD(+) and ECF(+) subjects tended to have lowest BMD. ECF may be more specific for assessing mild VF than the criteria based on vertebral deformity.     

Case–Control Study of Etiologic Factors in the Development of Severe Pelvic Organ Prolapse

The aim of this case–control study was to identify etiologic factors predictive for the development of severe pelvic organ prolapse. Three hundred and sixty-eight controls from a database describing pelvic organ support in the general population were identified as having known good pelvic organ support. Eighty-seven cases were identified from a urogynecology clinic with severe pelvic organ prolapse. The risk of severe prolapse was modeled using stepwise multiple logistic regression analysis. Additional analyses using χ² and two-sample t-tests were conducted to determine differences in means for individual variables. Variables examined included age, gravidity, parity, number of vaginal deliveries, weight of largest infant delivered vaginally, menopause status, race, body mass index prior to pelvic surgery, and medical illnesses. The following four variables were selected in the regression analysis as predicting severe prolapse: age, weight of largest vaginal delivery, hysterectomy and previous prolapse surgery. Other variables that demonstrated statistically significant differences between groups by χ² and two-sample t-tests were gravidity, parity, number of vaginal deliveries, menopausal status, race, history of incontinence surgery and the presence of hypertension. Variables that did not demonstrate any significant differences were body mass index, the presence of chronic obstructive pulmonous disease and diabetes mellitus. Advancing age, increasing weight of infants delivered vaginally, a history of hysterectomy and a history of previous prolapse surgery were found to be the strongest etiologic predictors of severe pelvic organ prolapse in our population.     

Adverse Reactions and Drug–Drug Interactions in the Management of Women with Postmenopausal Osteoporosis

The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug–drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug–drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.     

Effects of Treatment with Parathyroid Hormone 1–84 on Quantity and Biomechanical Properties of Thoracic Vertebral Trabecular Bone in Ovariectomized Rhesus Monkeys

Osteoporosis is characterized by impaired bone quality leading to increased susceptibility to fracture, particularly of the thoracic spine. However, the lumbar spine is studied most commonly. We investigated the effects of 16 months of treatment with full-length parathyroid hormone (PTH) 1–84 (5, 10, or 25 μg/kg) on bone mineral density (BMD) and on architecture and biomechanical properties of trabecular bone at the thoracic spine of ovariectomized (OVX) adult rhesus monkeys and compared the results with those from the lumbar spine. At baseline, 9 months after surgery, dual-energy X-ray absorptiometric BMD at T9–T12 was 7% lower in OVX than in sham animals. All PTH(1–84) doses increased BMD to sham levels within 7 months. Micro-computed tomography of T10 vertebrae showed that trabecular bone volume and connectivity were higher in PTH(1–84)-treated animals than in sham controls, primarily through a significantly greater trabecular number. Peripheral quantitative computed tomography of trabecular bone cores from T11 and T12 confirmed that PTH(1–84) increased BMD. Compression testing of the cores showed that PTH(1–84) treatment increased stiffness, modulus, yield load, and yield stress to levels significantly greater than in sham animals, with the largest effect in the 10 μg/kg group (35–54% greater than in OVX controls). Thus, PTH(1–84) treatment increased BMD and the biomechanical properties of trabecular bone at the thoracic spine of OVX rhesus monkeys. The 10 μg/kg dose produced the greatest effect on trabecular strength, possibly because the highest dose stimulated bone remodeling excessively. Importantly, the changes observed were similar to those in lumbar vertebrae, thereby validating extrapolation of results from the lumbar to the thoracic spine.     

Clinical Outcomes of Isobar TTL System with Isthmic Bone Grafting and Pedicle Screw‐Vertebral Plate Hook with Direct Repair of Defect for Lumbar Spondylolysis: A Matched‐Pair Case Control Study

Objective

Although direct isthmic repair, such as PSVPH, did not affect the mobility of the fixed segment and adjacent segment, it has a relatively low rate of isthmic fusion compared with conventional fusion. The Isobar TTL dynamic internal fixation system has been widely used in clinical practice and has achieved satisfactory clinical results. However, the use of the Isobar TTL system in combination with direct isthmic repair for lumbar spondylolysis has rarely been reported. The aim of this study was to compare the clinical and radiologic outcomes between patients who underwent Isobar TTL system and PSVPH with direct repair of defect for lumbar spondylolysis.

Methods

Stepwise propensity score matching (PSM) for age and sex were performed to keep comparable clinical data between groups in this retrospective and matched-pair case control study. A total of 50 patients diagnosed with lumbar spondylolysis underwent surgical implantation of the Isobar TTL group (n = 25) or PSVPH group (n = 25) from June 2009 to June 2016. Clinical outcomes were assessed using the Oswestry disability index (ODI), and visual analog score (VAS). Radiographic evaluations included range of motion (ROM) and the disc heights of stabilized segment and adjacent segment, adjacent segment degeneration (ASD) and bony fusion. Three-dimensional reconstruction of lumbar CT scan was obtained to evaluate bone fusion of the isthmic at final follow-up. The independent Student's t test and chi-square test were applied to compare the differences between groups.

Results

A total of 25 patients from TTL group were matched to 25 patients in PSVPH group for age, sex, body mass index (BMI), defect side, spondylolisthesis meyerding, and follow-up duration. The intervertebral space height (IH) of stabilized segment at postoperative 1 week and final follow-up in the TTL group was higher than those in the PSVPH group, respectively (P = 0.030; P = 0.013). The ROM of stabilized segment at final follow-up in the TTL group was significantly lower than that in the PSVPH group (P < 0.001). The bony fusion rate at the final follow-up was 88.0% (22/25 cages) in the TTL group and 80.0% (20/25 cages) in the PSVPH group. The ODI score at final follow-up in the TTL group was significantly lower than that in the PSVPH group (P = 0.007).

Conclusion

Overall, our data suggest that the Isobar TTL system outcomes are comparable to those in the PSVPH, with a similar high bony fusion rate as PSVPH, especially its wider indications as a new surgery.     

Global DNA Methylation Not Increased in Chronic Hemodialysis Patients: A Case–Control Study

Patients with chronic kidney disease have an increased risk of cardiovascular disease and mortality. Since DNA methylation is an important mechanism modulating the gene expression associated with aging, inflammation, and atherosclerosis, the objective of this study was to determine the possible effect of the uremic milieu on global DNA methylation and DNA methyltransferase (DNMT) expression in uremic status by comparing chronic hemodialysis (HD) patients with the normal population. Twenty normal subjects and twenty chronic dialysis patients with similar ages, sex, and body mass indexes (BMIs) were included. We evaluated the clinical characteristics; the levels of homocysteine, total indoxyl sulfate (IS), and total p-cresol sulfate (PCS); and the DNMT messenger RNA expression and global DNA methylation in the peripheral blood leukocytes. The chronic HD patients had significantly higher blood urea nitrogen (BUN), creatinine (Cr), uric acid, Ca, P, intact parathyroid harmone (iPTH), cholesterol, high-sensitivity C-reactive protein (hs-CRP), total indoxyl sulphate (IS) and p-cresol sulphate (PCS), and homocysteine than the normal subjects. The expression of DNMT 1 and 3a did not differ significantly between these two study groups. The chronic HD patients had significantly decreased DNMT 3b expression in the leukocytes. There were no significant correlations between the global DNA methylation and the levels of IS, PCS, and homocysteine. We concluded that chronic HD patients may have lower DNMT 3b expression than normal subjects. However, the status of global DNA methylation may not change significantly in uremic patients when compared with the normal population.     

Misclassification of Case–Control Studies in the Orthopedic Literature Is Common: A Bibliometric Analysis

Background

Observational studies constitute the majority of the orthopedic literature, each type distinct in terms of what it can and cannot measure. Case–control studies select participants based on outcome status, not exposure status, and therefore differ from other observational studies in their aims, limitations, and conclusions. Misclassification of a different kind of study as a case–control study can lead to misinterpretation of the data and misreporting of its level of evidence (LOE), either “overselling” or “underselling” its importance.

Questions/Purposes

We sought to answer three questions: (1) How frequently do studies reported to be orthopedic case–control studies actually reflect other study designs? (2) What factors might be associated with misclassification? (3) How does study design misclassification affect LOE reporting?

Methods

A bibliometric analysis was performed to identify all studies published in 75 orthopedic journals over a one-year period (January 2017 through December 2017) that included the term “case–control” in the title, abstract, or main text. We identified the proportion of studies that were misclassified as “case–control” in design and recorded the associated changes in reported LOE. We also examined associations between study misclassification (and by extension LOE misclassification) and the study specialty, journal specialty, and journal impact factor.

Results

Of 339 studies that reported a case–control design, 227 (67%) were misclassified and reflected other study designs. The study designs most often misclassified as case–control designs were retrospective cohort studies (n = 97; 43%) and cross-sectional studies (n = 88; 39%). The frequency of misclassification was associated with the subspecialty of the journal and the impact factor but not the study subspecialty. After correction of the LOE in the misclassified studies that reported an LOE (n = 193), it was found that 28 (15%) had underreported their LOE, and eight (4%) had overreported their LOE.

Conclusions

Studies reported in the orthopedic literature to have a case–control design frequently have another study design, and this pattern is consistent across subspecialties. Enhanced rigor in accurately defining study designs in orthopedics could be achieved through training and stricter review processes.

     

Early Discrimination Between Tumor-Induced Rickets/Osteomalacia and X-Linked Hypophosphatemia in Chinese Children and Adolescents: A Retrospective Case–Control Study

In children and adolescents, distinguishing tumor-induced rickets/osteomalacia (TIR/O) from hereditary hypophosphatemic rickets/osteomalacia (HR/O) is a medical challenge. We retrospectively studied 10 Chinese children and adolescents with TIR/O who underwent surgery at a mean age of 17.4 ± 2.1 years and compared their characteristics to 24 age- and sex-matched patients with X-linked hypophosphatemia (XLH). Positive family history of HR/O and dental problems, such as enamel hypoplasia and dental abscess, were reported in 8 (33.3%) and 5 (20.8%) patients with XLX, respectively, but not in patients with TIR/O. In addition, in comparison with XLH patients, TIR/O patients had an older disease onset age (150 versus 24 months, p < 0.001), a higher height standard deviation score (SDS; −1.2 ± 1.8 versus −4.0 ± 1.4, p < 0.001), a lower Z-score of bone mineral density (BMD) at lumbar spine (LS) (−3.9 [6.0] versus +1.8 [7.0], p < 0.001), and a higher serum intact fibroblast growth factor 23 (FGF23) level (500.27 ± 87.20 versus 121.71 ± 70.94 pg/mL, p < 0.001), corresponding to a lower serum phosphate level (0.52 ± 0.07 versus 0.64 ± 0.11 mmol/L, p = 0.005) and a higher serum alkaline phosphatase (ALP) level (557 [631] versus 305 [249] U/L, p = 0.005). We generated receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). The AUCs of onset age, FGF23, and LS Z-score were equal to 1, suggesting that these are excellent indices for the differential diagnosis between TIR/O and XLH. In summary, our study furthers our understanding of the spectrum of clinical, biochemical, and pathologic findings associated with TIR/O. For children and adolescent patients with HR/O, a comprehensive and careful clinical and laboratory evaluation is of great importance, and we recommend enquiry of the family history, onset age, and dental problems, as well as measurement of serum FGF23 and BMD. © 2021 American Society for Bone and Mineral Research (ASBMR).