Ping Chung Leung

Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur

BACKGROUND A number of recent case reports and series have identified a subgroup of atypical fractures of the femoral shaft associated with bisphosphonate use. A population-based study did not support this association. Such a relationship has not been examined in randomized trials. METHODS We performed secondary analyses using the results of three large, randomized bisphosphonate trials: the Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial (PFT). We reviewed fracture records and radiographs (when available) from all hip and femur fractures to identify those below the lesser trochanter and above the distal metaphyseal flare (subtrochanteric and diaphyseal femur fractures) and to assess atypical features. We calculated the relative hazards for subtrochanteric and diaphyseal fractures for each study. RESULTS We reviewed 284 records for hip or femur fractures among 14,195 women in these trials. A total of 12 fractures in 10 patients were classified as occurring in the subtrochanteric or diaphyseal femur, a combined rate of 2.3 per 10,000 patient-years. As compared with placebo, the relative hazard was 1.03 (95% confidence interval [CI], 0.06 to 16.46) for alendronate use in the FIT trial, 1.50 (95% CI, 0.25 to 9.00) for zoledronic acid use in the HORIZON-PFT trial, and 1.33 (95% CI, 0.12 to 14.67) for continued alendronate use in the FLEX trial. Although increases in risk were not significant, confidence intervals were wide. CONCLUSIONS The occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare, even among women who had been treated with bisphosphonates for as long as 10 years. There was no significant increase in risk associated with bisphosphonate use, but the study was underpowered for definitive conclusions.

The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: A Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long‐term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly–Pivotal Fracture Trial (HORIZON‐PFT) was extended to 6 years. In this international, multicenter, double‐blind, placebo‐controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent‐to‐treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN‐BMD remained constant in Z6 and dropped slightly in Z3P3 (between‐treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment. (ClinicalTrials.gov identifier: NCT00145327).

Modified Pfirrmann grading system for lumbar intervertebral disc degeneration.

Study Design. A reliability study was conducted. Objective. To modify a grading system for lumbar disc degeneration and to test the reliability of this modified grading system. Summary of Background Data. The 5-level Pfirrmann grading system for disc degeneration did not prove discriminatory when used to assess disc degeneration in the elderly spine. Such discriminatory power is necessary to test the association between other variables and severity of disc degeneration. Methods. An 8-level modified grading system for lumbar disc degeneration was developed including a description of the changes expected for each grade and a 24-image reference panel. The reliability of the modified grading system was tested on 260 lumbar intervertebral discs in 52 subjects (26 men, 26 female) with a mean age of 73 years (range, 67–83 years). All examinations were analyzed independently by 3 readers. Intraobserver and interobserver reliabilities were assessed by calculating weighted kappa statistics. Results. On average, for all 3 readers, 0.39% of the 260 discs were classified as Grade 2, 22% were classified as Grade 3, 21.5% were classified as Grade 4, 25.3% were classified as Grade 5, 19.1% were classified as Grade 6, 7.1% were classified as Grade 7, and 4.8% were classified as Grade 8. Intraobserver agreement was excellent (weighted kappa range, 0.79–0.91) with substantial interobserver agreement (weighted kappa range, 0.65–0.67). Complete intraobserver agreement was obtained, on average, in 85% of all discs with 84% of disagreement being as a result of a 1 grade difference. Complete interobserver agreement was obtained, on average, in 66% of all discs with 91% of disagreement being as a result of a 1 grade difference. Conclusion. The modified Pfirrmann grading system is useful at discriminating severity of disc degeneration in elderly subjects. The system can be applied with good intra- and interobserver agreement.

Associated factors and health impact of sarcopenia in older chinese men and women: a cross-sectional study.

Background: Sarcopenia is increasingly being recognized as a feature of frailty in old age and is associated with unfavorable health outcomes in Western populations. Little is known about sarcopenia among Asian elderly populations. Objectives: The study was undertaken to study the association between sarcopenia and common chronic illnesses, lifestyle factors, psychosocial well-being and physical performance. Methods: 4,000 community-dwelling Chinese elderly ≧65 years were recruited. Medical illnesses, cigarette smoking, alcohol consumption, physical activity level and psychosocial well-being scores were recorded. Physical performance measured included grip strength, timed chair-stands, stride length and a timed 6-meter walk. Muscle mass was measured using dual-energy X-ray absorptiometry. Relationships between appendicular skeletal muscle mass (ASM/ht2) and multiple variables were analyzed using uni- and multivariate analyses. Results: Mean ASM/ht2 was 7.19 and 6.05 kg/m2 in men and women respectively. Older age, cigarette smoking, chronic lung disease, atherosclerosis, underweight, and physical inactivity were associated with low adjusted ASM, which was in turn associated with poorer physical well-being in men. After adjustment to age, lower appendicular muscle mass was associated with weaker grip strength in both sexes. In men, lower limb tests (chair-stands, walking speed and step length) were not related to ASM, while in women, lower muscle mass was not associated with poorer lower limb muscle performance. Conclusions: Sarcopenia in community-dwelling older Chinese men and women was associated with cigarette smoking, chronic illnesses, underweight, physical inactivity, poorer well-being and upper limb physical performance.

An effective treatment of comminuted fractures of the distal radius

One hundred cases of comminuted fracture of the distal radius were treated by a simple uniform method consisting of distraction by an external fixator for 3 weeks followed by functional bracing. During the application of the external fixator, autogenous cancellous bone chips were taken from the iliac crest and packed into the fracture site to realign the juxtaarticular fragments and to fill up the bone gap. Complications have been minimal. The results, after an average follow-up period of 20 months, taking into consideration subjective assessment of pain, objective measurement of wrist motion, and radiologic angles, have been excellent.

Functional Decline in Cognitive Impairment - The Relationship between Physical and Cognitive Function

Background: Physical function decline is associated with dementia, which might either be mediated by the coexisting sarcopenia or directly related to the impaired cognition. Our objectives are to examine the relationship between cognitive function and performance-based physical function and to test the hypothesis that cognitive function is related to poor physical function independent of muscle mass. Methods: We measured muscle strength, performance-based physical function and muscle mass using dual-energy X-ray absorptiometry and cognitive function using the cognitive part of the Community Screening Instrument of Dementia (CSI-D) in 4,000 community-dwelling Chinese elderly aged >65 years. A CSI-D cognitive score of >28.40 was considered as cognitively impaired. The effect of cognitive impairment on muscle strength and physical function was analyzed by multivariate analysis with adjustment for age, appendicular skeletal mass (ASM), the Physical Activity Scale for the Elderly (PASE) and other comorbidities. Results: In both genders, the cognitively impaired (CSI-D cognitive score >28.40) group had a weaker grip strength (–5.10 kg, p < 0.001 in men; –1.08 kg in women, p < 0.001) and performed worse in the two physical function tests (in men, 6-meter walk speed, –0.13 m/s, p < 0.001, chair stand test, 1.42 s, p < 0.001; in women, 6-meter walk speed, –0.08 m/s, p < 0.001, chair stand test, 1.48 s, p < 0.001). After adjustment for age, ASM, PASE and other comorbidities, significant differences in grip strength (–2.60 kg, p < 0.001 in men; –0.49 kg, p = 0.011 in women) and the two physical function tests persisted between the cognitively impaired and nonimpaired group (in men, 6-meter walk speed, –0.072 m/s, p < 0.001, chair stand test, 0.80 s, p = 0.045; in women, 6-meter walk speed, –0.049 m/s, p < 0.001, chair stand test, 0.98 s, p < 0.001). Conclusions: Poor physical function and muscle strength coexisted with cognitive impairment. This relationship was independent of muscle mass. It is likely therefore that the functional decline in dementia might be related directly to factors resulting in cognitive impairment independently of the coexisting sarcopenia.

Fractured patella: operative treatment using the tension band principle.

The tension band principle was applied in the operative treatment of fractures of the patella in 139 patients, of which 100 were reviewed retrospectively; 61 per cent were males and 70 per cent were aged between 50 and 70. The fractures were treated soon after admission and movement of the knee was started as soon as possible after the operation. Sixty-eight patients were reviewed and 72 per cent were happy with the resulting knee function. Objectively, 81.3 per cent had an excellent or good result. Minor troubles from the operations were common but it was concluded that the wiring of fractured patellas using the tension band principle is a safe and effective technique.

Efficacy and tolerability of a Chinese herbal medicine concoction for treatment of atopic dermatitis: A randomized, double-blind, placebo-controlled study

Background  There has been considerable interest in traditional Chinese herbal medicine (TCHM) as a treatment for atopic dermatitis (AD). A twice‐daily concoction of an ancestral formula containing five herbs has been found to be beneficial in an open study.

Imaging of musculoskeletal tuberculosis: a new look at an old disease.

There are certain imaging features that help to differentiate tuberculosis from other bone and joint disorders with a similar presentation. The current authors discuss these distinguishing imaging features particularly with respect to ultrasound, computed tomography, and magnetic resonance imaging. The judicious and appropriate use of these newer imaging modalities coupled with aspiration or biopsy can lead to earlier recognition of musculoskeletal tuberculosis before the onset of debilitating disease.

FLUID CONDUCTANCE OF CANCELLOUS BONE GRAFT AS A PREDICTOR FOR GRAFT-HOST INTERFACE HEALING

The aim of this study is to test the hypothesis that the fluid conductance of cancellous bone graft is a deciding factor in graft-host union. Cylindrical cancellous bone specimens were trephined from fresh porcine femoral heads in a direction either parallel or perpendicular to the femoral neck axes. The graft after a defatting and freeze-drying process was placed in a perfusion apparatus. The pressure drop across the bone graft and the induced flow were measured and the conductance to fluid flow was calculated as the slope of the flow-pressure relation. Grafts of different flow conductance were transplanted into 35 rabbits to replace segments of tibiae. Nine weeks after grafting, 29 rabbits which had completed the follow-up without incidents were sacrificed. The decalcified sections of the grafts and the adjacent tibiae were examined microscopically for histological events during graft-host interface healing. Perfusion data indicated that fluid conductance ranged from 0.05 x 10(-10) to 13.4 x 10(-10) m3 s-1 Pa-1 and was higher in the direction parallel to the femoral neck axis, inversely proportional to the length of the graft and directly proportional to the square of porosity. Data from rabbit model supported the hypothesis stated above. A threshold conductance was found to be 1.5 x 10(-10) m3 s-1 Pa-1, below which revascularisation and the formations of osteoblasts and fibrous tissues could not be attained. How the low conductance led to non-union at the graft-host interface was briefly discussed.