Bone turnover markers reference database in five Southeast Asian countries.

Osteoporosis is highly prevalent, particularly in developing countries. However, bone turnover marker reference ranges for management of osteoporosis in Asian population are yet to be explored and established. Thus, this study aims to develop a regional bone turnover markers (BTMs) reference database by combining country-specific reference database from five ASEAN countries: Malaysia, the Philippines, Singapore, Thailand, and Vietnam. We established a healthy reference population of 746 healthy premenopausal women aged 20 to 44 years old. Serum Procollagen 1 N-Terminal Propeptide (P1NP), Osteocalcin (OC), and Beta-Crosslaps (CTX) concentrations were measured using an automated immunoassay analyzer system, the cobas® modular analyzer systems (Roche Diagnostic Gmbh). The reference interval was defined as the central 95 % range. The estimated reference interval for CTX was 128 to 811 ng/L, OC was 9.0 to 33.0 µg/L, and for P1NP, the range was 22.8 to 96.5 µg/L. Comparison across countries showed that Singaporeans had the highest levels of median CTX along with Thais and Filipinos, who had significantly higher levels of P1NP and OC. Exploratory analysis on the associations with age showed that BTMs decreased with increasing age at 20 to 29 years old and plateaued after 30 years old. When excluding participants in their 20s, the reference interval estimated were CTX: 117-678 ng/L, P1NP: 21.6-85.8 µg/L and OC: 3.5-27.0 µg/L respectively. To the best of our knowledge, this is the first study to report BTMs reference intervals based on a healthy premenopausal Southeast Asian population which will contribute to the appropriate assessment and monitoring of bone turnover rate in the evaluation and management of osteoporosis in the Southeast Asian region. LAY SUMMARY: Osteoporosis is a common health issue, especially in developing countries. However, there is a lack of information on bone health markers specific to the Southeast Asian population. This study aimed to fill this gap by creating a reference database for bone turnover markers (BTMs) in Southeast Asian countries, including Malaysia, the Philippines, Singapore, Thailand, and Vietnam. The researchers studied 746 healthy women aged 20 to 44 years and measured blood markers related to bone health. The reference interval, representing the normal range, was determined. For example, the normal range for CTX was found to be 128 to 811 ng/L, for Osteocalcin was 9.0 to 33.0 µg/L, and for P1NP, the range was 22.8 to 96.5 µg/L. When excluding participants in their 20s, the reference intervals estimated were CTX: 117-678 ng/L, P1NP: 21.6-85.8 µg/L and OC: 3.5-27.0 µg/L respectively. Comparing the results across countries, Singaporeans, Thais, and Filipinos showed variations in their biochemical bone marker levels. Additionally, the study observed changes in the levels with age, with a decrease in BTMs observed after the age of 30. This groundbreaking study provides the first-ever reference intervals for BTMs in a healthy premenopausal Southeast Asian population. These findings will help in the proper assessment and monitoring of bone health, contributing to the management of osteoporosis in the Southeast Asian region.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

2021 Asia-Pacific League of Associations for Rheumatology clinical practice guideline for treatment of gout.

BACKGROUND: Gout is the most prevalent inflammatory arthritis in the Asia-Pacific region and worldwide. This clinical practice guideline (CPG) aims to provide recommendations based on systematically obtained evidence and values and preferences tailored to the unique needs of patients with gout and hyperuricemia in Asia, Australasia, and the Middle East. The target users of these guidelines are general practitioners and specialists, including rheumatologists, in these regions. METHODS: Relevant clinical questions were formulated by the Steering Committee. Systematic reviews of evidence were done, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation methodology. A multi-sectoral consensus panel formulated the final recommendations. RESULTS: The Asia-Pacific League of Associations for Rheumatology Task Force developed this CPG for treatment of gout with 3 overarching principles and 22 recommendation statements that covered the treatment of asymptomatic hyperuricemia (2 statements), treatment of acute gout (4 statements), prophylaxis against gout flare when initiating urate-lowering therapy (3 statements), urate-lowering therapy (3 statements), treatment of chronic tophaceous gout (2 statements), treatment of complicated gout and non-responders (2 statements), treatment of gout with moderate to severe renal impairment (1 statement), and non-pharmacologic interventions (5 statements). CONCLUSION: Recommendations for clinically relevant scenarios in the management of gout were formulated to guide physicians in administering individualized care.

Intervention thresholds to identify postmenopausal women with high fracture risk: A single center study based on the Philippines FRAX model.

OBJECTIVES: This study is designed to estimate appropriate intervention thresholds for the Philippines Fracture Risk Assessment Tool (FRAX) model to identify postmenopausal women with high fracture risk. METHODS: Age dependent intervention thresholds were calculated for a woman of body mass index 25 kg/m2 aged 50-80 years with a previous fragility fracture without other clinical risk factors. Fixed thresholds were developed using a database of 1546 postmenopausal women who underwent dual-energy X-ray absorptiometry for clinical reasons. Major and hip fracture risks were estimated using clinical risk factors with and without bone mineral density (BMD) input. Women were categorized to high risk and low risk groups according to the age dependent thresholds. The best cut-points were determined considering the optimum sensitivity and specificity using receiver operating characteristic analysis. RESULTS: The age dependent intervention thresholds of major fracture risk ranged from 2.8 to 6.9% while hip fracture risk ranged from 0.4 to 3.0% between 50 and 80 years of age. Major fracture threshold of 3.75% and hip fracture threshold of 1.25% were the best fixed thresholds observed and non-inclusion BMD in the fracture risk estimations did not change the values. As a hybrid method, 3% major fracture and 1% hip fracture risks for those < 70 years old and age-dependent thresholds for those aged 70 years and above can be recommended. CONCLUSIONS: The intervention thresholds estimated in the current study can be applied to identify Filipino postmenopausal women with a high fracture risk. Clinicians should decide on the type of thresholds most appropriate.

Consensus of official position of IOF/ISCD FRAX initiatives in Asia-Pacific region.

The fracture risk assessment tool (FRAX(®)) has been developed for the identification of individuals with high risk of fracture in whom treatment to prevent fractures would be appropriate. FRAX models are not yet available for all countries or ethnicities, but surrogate models can be used within regions with similar fracture risk. The International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) are nonprofit multidisciplinary international professional organizations. Their visions are to advance the awareness, education, prevention, and treatment of osteoporosis. In November 2010, the IOF/ISCD FRAX initiative was held in Bucharest, bringing together international experts to review and create evidence-based official positions guiding clinicians for the practical use of FRAX. A consensus meeting of the Asia-Pacific (AP) Panel of the ISCD recently reviewed the most current Official Positions of the Joint Official Positions of ISCD and IOF on FRAX in view of the different population characteristics and health standards in the AP regions. The reviewed position statements included not only the key spectrum of positions but also unique concerns in AP regions.

Efficacy and tolerability of celecoxib in the treatment of acute gouty arthritis: a randomized controlled trial.

OBJECTIVE: To evaluate the analgesic efficacy of high-dose celecoxib in the treatment of moderate to extreme pain and inflammation associated with acute gouty arthritis. METHODS: A multinational, randomized, double-blind, double-dummy, active-controlled trial was done with patients (aged≥18 years) with acute gouty monoarthritis or oligoarthritis (onset of pain≤48 h before enrollment). Patients were treated for 8 days with 1 week followup and were randomized 1:1:1:1 to receive celecoxib 50 mg bid, celecoxib 400 mg (followed by 200 mg later on Day 1 and then 200 mg bid for 7 days), celecoxib 800 mg (followed by 400 mg later on Day 1 and then 400 mg bid for 7 days), or indomethacin 50 mg tid. RESULTS: Of 443 patients screened, 402 were randomized and 400 received treatment. Baseline demographics were comparable among treatments. Patients receiving high-dose celecoxib (800/400 mg) experienced a significantly greater reduction in pain intensity on Day 2 compared with low-dose celecoxib 50 mg bid [least squares (LS) mean difference -0.46; p=0.0014]. For high-dose celecoxib 800/400 mg, the change in pain scores from baseline to Day 2 was comparable with indomethacin 50 mg tid (LS mean difference 0.11; p=0.4331). There were significant differences in adverse events when the combined celecoxib groups (29.5%) were compared with patients taking indomethacin (43.1%; p=0.0116). There was no change in median serum creatinine levels for any treatment. There were more discontinuations due to adverse events (8.8% vs 3%; p=0.0147) with indomethacin than with the combined celecoxib groups. CONCLUSION: High-dose celecoxib (800/400 mg) was significantly more effective than low-dose celecoxib (50 mg bid) and comparable to indomethacin in the treatment of moderate to extreme pain in patients with acute gouty arthritis. Further, celecoxib was well tolerated.

Consensus statements on osteoporosis diagnosis, prevention, and management in the Philippines.

OBJECTIVE: The consensus statements were developed to assist healthcare practitioners in providing optimal care to postmenopausal individuals at risk for osteoporosis and fragility fractures in the local setting. METHODOLOGY: The Technical Review Committee formed by the Osteoporosis Society of the Philippines Foundation Inc. in cooperation with the Philippine Orthopedic Association drafted, retrieved available published evidence, and appraised important issues on osteoporosis and fragility fractures. The Appraisal of Guidelines Research and Evaluation instrument was used to appraise published guidelines while a systematic way of validating the quality of evidence and the level of recommendation was done using the GRADE system. A multidisciplinary panel of experts and stakeholders in an en banc meeting conferred and approved the recommendations. RESULTS AND CONCLUSION: There were five key issues on preventive, seven on diagnostic, nine on therapeutic aspects of osteoporosis with four other surgical concerns on fragility fractures. All were approved by a panel of stakeholders through a majority vote. These statements will best inform the clinicians and the specialists including orthopedic surgeons and general care practitioners on issues of postmenopausal Filipino women at risk for osteoporosis and fragility fractures.

High-calcium milk prevents overweight and obesity among postmenopausal women.

BACKGROUND: The Sixth National Nutrition Survey 2003 revealed that the highest prevalence of overweight and obesity among Filipino female adults (30.8%) was found in the age group from 40 to 59 years. Obesity is associated with a number of chronic diseases, including cardiovascular disease, hypertension, and diabetes. Low calcium intake has been identified as a potential contributing factor to overweight and obesity. OBJECTIVE: To assess the effect of a high-calcium,fortified, low-fat milk drink with added vitamin D versus a low-calcium placebo drink on anthropometric measurements of postmenopausal women. METHODS: Women who were at least 5 years postmenopausal were invited to participate in the study. Potential participants underwent three stages of screening: initial interview, dual-energy x-ray absorptiometry, and blood testing for biochemical screening. Anthropometric indices were measured at baseline and the end of the study. Sixty women were qualified to participate in the study. The women were randomly assigned to two groups, one of which received 400 ml of the high-calcium milk daily for 16 weeks while the other received the placebo drink. RESULTS: No significant increases were observed in the anthropometric indices of the subjects receiving the high-calcium fortified milk at the end of the study. However, there were significant increases in the weight (p = .008), body mass index (p = .007), and waist (p = .018) and hip (p = .003) circumferences of the subjects receiving the placebo drink. CONCLUSIONS: A change in dietary calcium intake may be a useful measure as part of an overall approach to prevent the occurrence of overweight and obesity among postmenopausal women.

The effect of a fortified milk drink on vitamin D status and bone turnover in post-menopausal women from South East Asia.

Calcium and vitamin D are essential for bone growth; milk is an appropriate vehicle to be fortified with calcium, vitamin D and other minerals. The purpose of the current study was to compare the effect of supplementing with a high calcium milk drink with added vitamin D, magnesium and zinc (HCM) versus a placebo drink on serum parathyroid hormone (PTH) and vitamin D status as well as markers of bone formation/resorption in postmenopausal women living in South East Asia (Jakarta, Indonesia and Manila, the Philippines) over a period of 4 months. Calcium intake at baseline was 237 mg (median; 176-316, interquartile range) for Indonesia and 353 mg (median; 222-480, interquartile range) for the Filipino women per day. Fortified milk supplementation reduced the percentage of women that were insufficient in 25 (OH) vitamin D(3) (<50 nmol/L) from 70% to 22% in the Indonesian women and 20% to 0% in the Filipino women. Fortified milk supplementation significantly reduced parathyroid hormone levels (PTH) by week 2 (22% and 11%), C-telopeptide of type I collagen (CTX) by week 2 (34% and 27%), osteocalcin (OC) by week 8 (18% and 25%) and procollagen type I N-propeptide (PINP) by week 8 (15% and 21%), in women from Indonesia and the Philippines, respectively. Thus, the HCM intervention was able to significantly improve vitamin D status, lower PTH levels and reduce bone turnover in two groups of South East Asian women.

Survey of vitamin D levels among post-menopausal Filipino women with osteoporosis.

OBJECTIVE: To determine the prevalence of vitamin D inadequacy in a group of Filipino post-menopausal women with osteoporosis. METHODS: Seventy otherwise healthy post-menopausal Filipino women seen at the University of Santo Tomas Hospital, Section of Rheumatology, were diagnosed with osteoporosis by central dual-energy X-ray absorptiometry (DXA) technique. Levels of serum 25-hydroxyvitamin D were measured using enzyme-linked immunosorbent assay. RESULTS: The mean age of this population was 70 +/- 8 years, with an average of 22 +/- 10 years since menopause, and mean body mass index (BMI) of 22 +/- 1 kg/m(2). Only 30% (21/70) were on calcium plus vitamin D supplementation. Overall serum 25-hydroxyvitamin D levels ranged from 48-128 nmol/L, with a mean of 87 +/- 20.48 nmol/L. Serum 25-hydroxyvitamin D levels were divided as follows: 80-140 nmol/L (adequate), 25-79 nmol/L (inadequate/insufficient), and < 25 nmol/L (deficient). Sixty-four percent (45/70) of subjects had adequate levels while 36% (25/70) had inadequate levels of 25-hydroxyvitamin D. There were no subjects with deficient levels of 25-hydroxyvitamin D. Fischer's exact test did not show a significant association between BMD and 25-hydroxyvitamin D (P = 0.4804). CONCLUSION: Among this group of women with post-menopausal osteoporosis, only 36% had insufficient levels of 25-hydroxyvitamin D, with none of the subjects having deficient 25-hydroxyvitamin D levels. The majority (64%) had normal serum 25-hydroxyvitamin D levels--comparatively higher than that reported in the literature. These results suggest the possible contribution of factors other than vitamin D deficiency in post-menopausal Filipino women with osteoporosis.

Does prolonged systemic glucocorticoid use increase risk of tophus formation among gouty arthritis patients?

AIM: To determine the relationship of steroid use with tophus formation and other comorbid conditions among male gout patients. METHODS: Review of medical records of Filipino gout patients under the care of rheumatologists was conducted. Univariate analysis (chi-square, Student's t-test) and multiple logistic regression analysis were performed to establish the risk for tophus formation among glucocorticoid users. Bivariate analysis was separately done to determine the confounding effect of steroid use in the association of comorbidities and tophi formation. RESULTS: There were 295 Filipino men with a mean age of 56 years and a mean duration of 12 years of gouty arthritis who were included in the study. Multivariate analysis showed a five times higher likelihood (OR 4.81 95% CI 1.92-12.04, P < 0.001) for tophus formation among prolonged steroid users. Confounders identified were disease duration of gout (> or = 10 years), presence of chronic kidney disease (CKD) and elevated serum creatinine level (SCr). Bivariate analysis of comorbidities showed that steroid use introduced a considerable bias in the relationship of hypertension, elevated SCr, CKD and dyslipidemia. CONCLUSION: Patients with equivalent prednisone intake of at least 15 mg/week for > or = 3 months is associated with tophi formation. In the presence of hypertension, renal impairment, and elevated serum creatinine level, use of steroids confounds the individual risk that each factor carries.

A rare case of Paget's disease of the bone in the Philippines.

A 40-year-old Filipina presented with a 2-year history of progressive bilateral inguinal and hip pain with limited range of motion. She had a bad fall which led to widespread body pains for 6 months partially relieved on multiple analgesic and anti-inflammatory agents. There was progressive weight loss and anemia. Focused musculoskeletal examination revealed moderate degree of generalized muscle atrophy, pain-limited range of motion of bilateral hip and shoulder joints, with equivocal muscle strength of both proximal and distal muscle groups of all extremities. Metastatic bone disease was ruled out when skeletal survey disclosed mixture of osteolytic and osteoblastic lesions, predominantly osteoblastic, on multiple sites. Bone turnover markers were elevated. Bone biopsy revealed histopathologic results compatible with Paget's disease of the bone. Management included oral calcium and vitamin D supplement followed by parenteral zoledronic acid, and a rehabilitation program. Four months after bisphosphonate therapy, the patient reported significant relief of symptoms with complete resolution of the previously noted generalized body pains, although she ambulates with use of an assistive device. Due to the rarity of the condition among Filipinos, this case was a diagnostic dilemma in itself, as it is most likely the first published case in the Philippine literature.

Validation of OSTA among Filipinos.

Osteoporosis is the most common metabolic bone disease in humans. It is a special concern not only among postmenopausal women, but men as well. In developing countries where there are meager resources, it will definitely be helpful to search for ways to identify patients with low bone mineral density who have a high risk of future fractures. These people need to be identified for treatment consideration in order to reduce the incidence of the disease and its complications. A simple risk index called the Osteoporosis Screening Tool for Asians (OSTA), based only on two variables, age and body weight, performed well in identifying the risk of osteoporosis among postmenopausal women. This index has been validated in Japan, Korea and other Caucasian populations as a useful tool in identifying individuals who will require BMD measurement. This is the first study that validated the said index in 1,597 Filipino women and men referred to a tertiary center for BMD measurement. It had sensitivity of 97 and 90% and specificity of 59 and 66% with areas under the curve of 0.8506 and 0.8475, respectively, for women and men. We conclude that OSTA performed just as well or even better than other indices used in other populations to identify individuals who are at varying degrees of risk for osteoporosis. The tool also proves to be a useful and practical guide to help clinicians to be more prudent and judicious in employing bone mineral density measurement.