Open-label study of treatment with alendronate sodium plus vitamin D in men and women with osteoporosis in Thailand.

BACKGROUND: It is generally believed that Thai people do not suffer from hypovitaminosis D because there is abundant sunlight throughout the year, and that taking vitamin D supplements could result in abnormally high levels of vitamin D. This is a Thai FDA-driven study to investigate this risk over a period of 26 weeks of taking alendronate sodium/vitamin D3 combination tablets. METHODS: Osteoporosis patients in Thailand were recruited to a multicenter, open-label, 6-month trial of oral alendronate sodium 70 mg/vitamin D3 5600 IU. Patients received study medication once a week for 26 weeks. Serum 25-hydroxyvitamin D (25(OH)D) and Beta-CrossLaps (ß-CTx) levels were measured at baseline and 26 weeks. The primary endpoint was the proportion of patients with 25(OH)D ≥ 50 ng/mL at week 26; it was hypothesized that 26 weeks' treatment would not result in 25(OH)D serum levels ≥ 50 ng/mL in > 7% of osteoporosis patients. RESULTS: One hundred ninety-eight patients were recruited. At baseline, 67.2% of the patients had 25(OH)D < 30 ng/mL; this declined to 34.4% by week 26. The mean 25(OH)D level improved from 27.8 ng/mL at baseline to 33.6 ng/mL at week 26. Five patients (2.69% of the full analysis set) had 25(OH)D levels ≥ 50 ng/mL at 26 weeks. The highest 25(OH)D level, 64.3 ng/mL, was observed in a patient whose baseline level was 102.2 ng/mL. The majority (62.9%) of the patients had optimal 25(OH)D levels (30-50 ng/mL). ß-CTx levels were reduced by 57.7% after 26 weeks' treatment. No clinically significant cases of hypercalcemia which could be associated with hypervitaminosis D were identified during physical examination, in vital signs, or in laboratory results. Overall, 73 patients (36.9%) reported at least one adverse event (AE), with 13 (6.6%) reporting drug-related AEs. Four patients discontinued due to AEs, two of which were drug-related. Serious AEs were reported for four patients, of which one was considered drug-related. CONCLUSIONS: Oral alendronate sodium 70 mg plus vitamin D3 5600 IU once weekly had an acceptable safety profile in this study, and increased serum 25(OH)D and reduced ß-CTx levels in osteoporosis patients. This treatment improved 25(OH)D levels, without causing abnormally high levels, after 26 weeks' treatment. TRIAL REGISTRATION: Clinical Trials.gov NCT01437111 , Registered September 19, 2011.

Association between the severity of knee osteoarthritis and serum cartilage biomarker levels.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. However, there has been no cost-effective tool for the investigation of the severity and progression of the disease because using OA standard diagnostic methods causes cartilage damage. OBJECTIVE: To evaluate the relationship between serum chondroitinsulphate WF6 (CS-WF6) and hyaluronate (HA) and the severity of knee OA according to Kellgren-Lawrence (K/L) grades of radiographic severity and minimal joint space width (JSWV). MATERIAL AND METHOD: One-hundred and twenty-six patients with OA (knee) according to K/L grades were classified into four groups. The JSW of the tibiofemoraljoint were measured from standing PA radiographs. Serum CS-WF6 and HA were analyzed by the ELISA based technique. One-way analysis of variance, Bonferroni's method and Kendall's tau coefficient relation test were performed to evaluate the association of K/L grades and JSW with levels of CS-WF6 and HA, respectively. RESULTS: Serum CS-WF6 levels in grade 4 were significantly increased when compared with the other grades (p < 0.05). The serum HA level did not show any significant difference among the grades of severity. The serum CS-WF6 level showed a significant negative correlation with the JSW and its levels rose rapidly to the level beyond 300 ng/ml. There was no correlation found between the levels of serum HA and JSW CONCLUSION: WF6 levels may be useful in identifying patients at risk of rapid progression reflected by a point of an abruptly high WF6 level. The determination of WF6 in the serum showed increasing levels in more severe grades, so it could be useful in monitoring the effectiveness of treatment. There were some limitations because of broad distribution and overlap with the normal range. Thus, it may not be suitable as a diagnostic tool.

Correlation of proximal femoral bone geometry from plain radiographs and dual energy X-ray absorptiometry in elderly patients.

BACKGROUND: Fracture prevention in osteoporotic patients is the primary treatment goal in assessing bone mineral density, identification of fracture risk, and determination of who should be treated. The literature shows that parameters of proximal femoral bone geometry such as hip axis length, femoral neck shaft angle (FNA), femoral neck width (FNW) and femoral neck cortical thickness (FNCT) can predict the risk of hip fracture. Those parameters are presented automatically with dual energy X-ray absorptiometry (DXA) scans, which are available in well-equipped hospitals. OBJECTIVE: To determine the correlation between proximal femoral bone geometry and the parameters from DXA scans and those from plain radiographs. MATERIAL AND METHOD: Forty-eight patients with no previous hip fractures or history of secondary osteoporosis underwent both a DXA scan of the hip area and a plain hip radiograph done in the same position, 25 degrees internal rotation. Bone geometries from both groups were measured to determine the correlation using Pearson correlation coefficient. RESULTS: Correlation between the parameters HAL, FNA, FNW andFNCT from the DXA scans and from the measurement of the plain radiograph was significant (p < 0.01) and the level of correlation was moderate to high. The FNCT had least mean difference (0.04). In addition, the parameter FNCT less than 0.29 mm in both DXA scans and plain radiographs, showed a significant correlation with osteoporosis (T-score <-2.5). CONCLUSION: The bone geometry parameters from either DXA scans orplain radiographs may be used to predict osteoporotic hip fracture with a moderate to high correlation. Plain radiographs are very helpful when DXA scan results are not available. The FNCT parameter has a strong correlation with osteoporosis.

Factors related to mortality after osteoporotic hip fracture treatment at Chiang Mai University Hospital, Thailand, during 2006 and 2007.

OBJECTIVE: To investigate the one-year mortality rate after osteoporotic hip fracture and to identify factors associated with that mortality rate. MATERIAL AND METHOD: A retrospective review of 275 osteoporotic patients who sustained a low-trauma hip fracture and were admitted in Chiang Mai University Hospital during January 1, 2006 to December 31, 2007 was accomplished. Eligibility criteria were defined as age over 50 years, fracture caused by a simple fall and not apathologicalfracture caused by cancer or infection. Results of this one-year mortality rate study were compared to studies of hip fracture patient mortality in 1997 and the period 1998-2003. RESULTS: The average one-year mortality rate in 2006-2007 was 21.1%. Factors correlated with higher mortality were non-operative treatment, delayed surgical treatment, and absence of medical treatment for osteoporosis. The 2006-2007 mortality rate was slightly higher than for the 1997 and 1998-2003 periods. CONCLUSION: The one-year mortality rate after osteoporotic hip fracture of 21.1% was approximately 9.3 times the mortality rate for the same age group in the general population, indicating that treatment of osteoporosis as a means of helping prevent hip fracture is very important for the individual, the family, and society as a whole.

Results of shortened program of Ponseti technique for congenital clubfoot.

OBJECTIVE: To study the results and complications of congenital clubfoot treatment using a shortened (twice a week) program of serial casting using Ponseti technique. MATERIAL AND METHOD: Sixteen patients with congenital clubfoot (26 feet) were treated by serial manipulation and casting twice a week until acceptable deformity correction (60 degrees of abduction with or without equinus deformity) were achieved RESULTS: Seventeen patients (65%) required less than three weeks in treatment to improvement in the deformity, while eight patients (30%) required more than three weeks of treatment. This period of treatment is at least two weeks shorter than the conventional Ponseti technique. One patient did not complete treatment due to hospital-acquired pneumonia. Four patients who developed pressure ulcers from the castings were continued in treatment and all achieved successful correction. CONCLUSION: A shortened program of clubfoot correction using the Ponseti technique can be effective for correcting uncomplicated clubfoot without serious complications.

Changes in the serum cartilage biomarker levels of healthy adults in response to an uphill walk.

INTRODUCTION: To prevent long-term unfavourable consequences to the articular cartilage of weight-bearing joints, serum biomarkers can be used to identify optimum loading of activities. This study aimed to investigate the circulation pattern of serum cartilage biomarkers in healthy adults in response to an uphill walk. METHODS: This study recruited 58 healthy participants for the experimental group and 24 matched participants for the control group. Participants in the experimental group walked continuously for 14 km on a pathway with a 5.97° incline, while participants from the control group walked on a horizontal pathway. Serum was collected from both groups preactivity (i.e. T1), immediately after activity (i.e. T2) and 24 hours after T1 (i.e. T3). The serum cartilage oligomeric matrix protein (COMP), chondroitin sulfate-WF6 (WF6) and hyaluronic acid (HA) levels at each time point were quantified using enzyme-linked immunosorbent assays, and the results analysed. RESULTS: Both groups shared similar demographic characteristics and activity duration. At T2, the serum COMP level of the experimental group was significantly higher than that of the control group, but the serum HA level of the experimental group was significantly lower than that of the control group. No significant difference between the serum WF6 levels of the experimental and control groups was observed at T2. CONCLUSION: Increasing levels of serum COMP demonstrate articular cartilage susceptibility to the increasing load. An unsustainable, high serum COMP level and an undetectable change in WF6 level were considered to be a reversible physiological change of the cartilage. A change in ser um HA level could be related to intensive physical activity and dynamic clearance rather than a change in cartilage structure.

Anatomical variations of the saphenous and descending genicular artery perforators: cadaveric study and clinical implications for vascular flaps.

BACKGROUND: With increasing use of free vascular flaps of the saphenous artery and descending genicular artery, the authors investigated the anatomical variations in cadavers. METHODS: Thirty-one fresh cadaveric thighs were studied by anatomical dissection. The perforators and their source arteries were skeletonized along their courses to the superficial femoral artery and measured. The perforators' nomenclature and abbreviations were modified from the Gent consensus. The skin and bone perforators were evaluated for their role in skin, bone, and osteocutaneous flaps. RESULTS: The descending genicular artery was noted in 27 thighs (87 percent) and gave rise to at least one skin perforator that could be used to develop an osteocutaneous flap. The chimeric pedicle length increased and the chimeric arm length decreased, as the descending genicular artery skin perforators were more distally located. The saphenous artery was noted in all 31 thighs, and in 16 (52 percent) it originated from the superficial femoral artery. Most musculocutaneous perforators of the saphenous artery were associated with the sartorius, whereas those of the descending genicular artery were associated with the vastus medialis. Superficial femoral artery skin perforators were noted in 10 thighs (32 percent). Two clinical cases, illustrating the use of the descending genicular artery vastus medialis perforator flap and of the distal-direct perforator osteocutaneous flap, are reported. CONCLUSIONS: This study investigated the anatomical variations in the skin and bone perforators of the medial knee. Free skin or bone flaps were achieved in all specimens and osteocutaneous chimera flaps were achieved in 87 percent of the thighs.

Increasing incidence of hip fracture in Chiang Mai, Thailand.

Hip fracture is a major health problem in Thailand. This study attempted to examine the incidence, related factors, and trends of hip fracture in Chiang Mai, Thailand. All hip fracture data among patients aged 50 yr or older were collected from hospitals in Chiang Mai, Thailand from August 1, 2006 to July 3, 2007. Data from the 1997 Chiang Mai hip fracture study were used for comparison. In the study period, 690 hip fractures were reported: 203 males and 487 females (male to female ratio was 1 to 2.4), with a mean age of 76.7 yr. The estimated cumulative incidence was 181.0 per 100,000, and the adjusted incidence was 253.3 (males: 135.9; females: 367.9). A simple fall was the most common mechanism (79%) of fracture, and 80% of the hip fractures occurred in patients aged 70 yr or older. The highest incidence of hip fracture was observed in patients older than 85 yr (1239). At 6 mo postfracture, most patients (61%) used a walking aid. Compared with the 1997 data, hip fracture incidence had increased by an average of 2% per yr, and the incidence of hip fracture had increased significantly from August 1, 2006 to July 31, 2007, especially in patients older than 75 yr. In patients older than 84 yr, the incidence increased by a factor of 2. Urgent strategies for the prevention and treatment of osteoporosis, and hence hip fracture, are needed.

Dysplasia epiphysealis hemimelica: a huge articular mass with unpredictable surgical results.

Dysplasia epiphysealis hemimelica or Trevor's disease is a rare disorder of localised osteochondral overgrowth affecting the epiphysis of extremities. This paper reports a 12-year-old boy presenting with a large bony mass at the left ankle diagnosed as dysplasia epiphysealis hemimelica. The articular surface of the ankle joint of the patient was evaluated with preoperative and postoperative MRIs. The 2-year postoperative MRI showed early osteoarthritis of the ankle, therefore demonstrating the importance of early excision avoiding more complex resections of intra-articular lesions.

Relationships between serum biomarker levels and clinical presentation of human osteosarcomas.

BACKGROUND: Currently, serum biomarkers play an important role as sensitive tools for monitoring the cancer development and progression. Each biomarker represents a specific pathogenesis and has different predictive capability. In order to identify their characteristics in human osteosarcoma, multiple potential biomarkers were analyzed simultaneously with clinical presentations. MATERIALS AND METHODS: Blood samples were collected from 28 osteosarcoma patients and 30 healthy matched controls. Specific clinical presentations were recorded, including: tumor volume, estimated based on three-dimensional MRI volumetric measurement; metastasis status; and histological cell types. Serum biomarkers analyzed by ELISA-based assays were bone-specific alkaline phosphatase (BALP), vascular endothelial growth factor (VEGF), hyaluronic acid (HA) and chondroitin sulfate WF6 (WF6). Serum lactate dehydrogenase (LDH) was analyzed by a photometric-based system. RESULTS: Serum BALP, LDH and WF6 levels of osteosarcoma patients were significantly higher than those of healthy controls, whereas HA and VEGF levels were not significantly different between the two groups. Serum BALP and LDH were positively correlated with tumor volume, (correlation coefficients 0.5 and 0.4, respectively). Serum BALP from metastasis and osteoblastic subtype group had a significantly higher level than that found in non-metastasis and non-osteoblastic subtypes group, respectively. Upon multivariate analysis, tumor volume was the only factor which correlated with BALP levels. CONCLUSION: Of the biomarkers analyzed in this study, serum BALP was the most reliable and sensitive for estimating tumor volume. A high level of serum WF6 reflects alteration of the extracellular matrix component of tumors. Both serum biomarkers can be expected to be further explored for use in specific clinical monitoring.

Long-term mortality after osteoporotic hip fracture in Chiang Mai, Thailand.

The purpose of the study was to investigate 10-yr mortality and associated factors after osteoporotic hip fracture. A prospective cohort study of mortality and associated factors was carried out in patients who sustained hip fracture and were admitted to Chiang Mai University Hospital from 1998 through 2003. Eligibility criteria were defined as age over 50yr, hip fracture caused by simple fall, and Singh index of 3 or less.Mortality rates at 3, 6, 12, 24, 36, 60, 96, and 120mo were 10%, 14%, 18%, 27%, 32%, 45%, 55%, and 68%, respectively. One-year mortality rates were 31% in males and 16% in females. The median survival time was 6yr. Ten-year mortality was 68%. Factors correlated with higher mortality were male gender, age greater than 70yr, and nonoperative treatment. Mortality after osteoporotic hip fracture in Thais was extremely high, especially in the first year. It was about 8 times higher than that in the age-adjusted general population.

Prospective evaluation of serum biomarker levels and cartilage repair by autologous chondrocyte transplantation and subchondral drilling in a canine model.

INTRODUCTION: The purpose of this study was to evaluate serum chondroitin sulfate (CS) and hyaluronic acid (HA) levels and the capability of cartilage repair of full-thickness cartilage defects after treatment with two different fundamental surgical techniques: autologous chondrocyte transplantation (AC) and subchondral drilling (SD). METHODS: A 4-mm-diameter full-thickness cartilage defect was created in each of 10 skeletally mature male outbred dogs. The dogs were randomly separated into two groups. Groups A and B were treated with AC and SD, respectively. An evaluation was made at the 24th week of the experiment. Serum was analyzed prospectively--preoperatively and at 6-week intervals--for CS and HA levels by enzyme-linked immunosorbent assay (ELISA) and ELISA-based assays, respectively. RESULTS: The cartilage repair assessment score (median +/- standard deviation) of group A (9.5 +/- 2.5) was significantly higher than that of group B (2.5 +/- 1.3) (P < 0.05). Group A also demonstrated a better quality of hyaline-like cartilage repair. Prospective analysis of serum WF6 and HA levels between the two groups did not show any significant difference. Serum WF6 levels at the 24th week of the experiment had a negative correlation (r = -0.69, P < 0.05) with the cartilage repair assessment score, whereas serum HA levels tended to correlate positively (r = 0.46, 0.1

Chondroitin sulfate epitope (WF6) and hyaluronic acid as serum markers of cartilage degeneration in patients following anterior cruciate ligament injury.

Serum chondroitin sulfate epitope (WF6) and hyaluronic acid (HA) levels were determined to be of clinical relevance to an anterior cruciate ligament (ACL) injury. This cross-sectional study recruited participants from two distinct groups. Group A was comprised of 74 healthy controls, and group B consisted of 33 ACL injury patients. Serum samples were taken and assayed by a competitive immunoassay with monoclonal antibody WF6. Serum HA was also determined by an ELISA-based assay using biotinylated HA-binding proteins. Both groups A and B shared similar values of age, body mass index, white blood cell count and percentage of polymorphonuclear cells. ESR levels were also shown to be within normal limits. The serum WF6 epitope levels of group B were significantly higher than those of group A, whereas serum HA levels were not different between the two groups. The serum WF6 epitope level is more sensitive to changes in articular cartilage due to a non-inflammatory instability condition than the serum HA level, and should prove to be one of the most promising assays for early post-traumatic arthritis detection.

Impact of bone marker feedback on adherence to once monthly ibandronate for osteoporosis among Asian postmenopausal women.

AIM: This study assesses the impact of serum carboxy-terminal collagen crosslinks (CTX) bone marker feedback (BMF) on adherence to ibandronate treatment in Asian postmenopausal women with osteoporosis. METHODS: This was a 12-month (6-monthly phased), randomized, prospective, open-label, multi-center study conducted in 596 (of 628 enrolled) postmenopausal women with osteoporosis (< or = 85 years old) who were naïve, lapsed, or current bisphosphonate users. Patients were randomized into two arms: serum CTX BMF at 3 months versus no-BMF. Once-monthly 150 mg ibandronate tablet was administered for 12 months and adherence to therapy was assessed at 6 and 12 months. In addition, patient satisfaction and safety of ibandronate treatment were also assessed. RESULTS: Serum CTX BMF at 3 months showed no impact on adherence. The proportions of adherent patients were comparable in the BMF versus no-BMF arms (92.6%vs. 96.0%, P = 0.16); overall, serum CTX levels were similar for adherent and non-adherent patients. However, BMF patients felt more informed about their osteoporosis (P < 0.001) and more satisfied (P < 0.01) than no-BMF patients. CONCLUSIONS: The Asian postmenopausal osteoporosis patients in this study had a high adherence rate to once-monthly ibandronate therapy. Use of serum CTX BMF had no further impact on increasing adherence, but increased treatment satisfaction.

Periosteal chondroma of the proximal humerus: a case report and review of the literature.

Periosteal chondroma is a slow growing benign cartilaginous tumor of bone. It is rarely reported among Thai people. The authors present a case ofperiosteal chondroma of the proximal humerus. A 14-year-old girl was admitted with a painless mass around her left shoulder On magnetic resonance images, a subcutaneous lesion with hypointensity on TI-weighted images and marked hyperintensity on T2-weighted images, eroded the underlying cortical bone of the proximal humerus. The patient underwent marginal excision. There was no recurrence of the lesion during 3 years of follow-up.

Epidemiology of hip fracture in Chiang Mai.

The incidence of hip fracture varies worldwide. From 1997 to 1998, the incidence of hip fracture in Chiang Mai was 151.2 and 185.2 per 100,000 from the hospital survey and the community survey respectively. The mortality rate in hospital following hip fracture was 2.1% and the one-year mortality rate rose steadily to 37%. In addition, morbidity after hip fracture may also carry serious implications on the functional independence and quality of life. Concerning the costs for treatment, hip fracture is also a great burden for the health service in Thailand. The risk factors for hip fracture include age, medical co-morbidities, current use of antihistamine, history of fracture, alcoholic consumption, low calcium intake and lack of physical activity, whereas calcium intake and physical activity were demonstrated as important protective factors against hip fracture. Improved understanding for epidemiology of hip fracture in Thailand could enhance the effectiveness for prevention of the fracture.