Efficacy and safety of Menatetrenone-4 postmenopausal Thai women.

Clinical and comparative study of the efficacy and adverse events of Menatetrenone-4. The control group (n=40) received elemental calcium carbonate 800 mg/day and the Menatetrenone-4 treated group received elemental calcium carbonate 800 mg/day plus vitamin K2 45 mg/day (n=43). The vitamin K2 treated group showed a marked decrease of undercarboxylated osteocalcin at 2 weeks, six months (51.52% p=0.0001) and twelve months (87.26% p=0.0001) compared to the calcium treated group. At the end of the sixth and twelve months both groups did not increase bone mass of the hip but the vitamin K2 treated group increased 0.6 per cent of bone mass of the lumbar spine and decreased bone resorption 65.42 per cent (p=0.0001) compared to the calcium treated group. The calcium treated group was switched to the vitamin K2 treated group at the end of six months and showed a decrease of the level of undercarboxylated osteocalcin the same as the former vitamin K2 treated group. The adverse events were 2 cases of mild skin rash which subsided after cessation of medication.

Study of the level of biochemical bone markers: NMID osteocalcin and bone resorptive marker (beta CTx) in Thai women.

Study of the level of NMID osteocalcin and Beta CTx in 700 Thai women. The mean of NMID osteocalcin = 21.45 SD = 11.18 95% CI = 20.12 to 22.79 ng/ml and betacrosslap = 0.445 ng/ml SD = 0.25 with 95% CI = 0.414 to 0.478 ng/ml in women who menopaused less than 10 years ago (n=237), these values were higher than in young adult females (n=63) and menstruating women (n=123) which was statistically significant (p=0.0001). The value of both bone markers in elderly women who had menopaused more than 10 years ago and were aged more than 60 years (n=94) showed a marked increase of NMID osteocalcin, 25.63 ng/ml SD = 14.22 ng/ml but the value of betacrosslap was below the young-menopausal women, 0.394 ng/ml SD = 0.241 ng/ml 95% CI = 0.344 to 0.444 ng/ml. Menopausal women are at a high risk of osteoporosis due to high bone turnover. In our study, the NMID osteocalcin had a high correlation with betacrosslap (r=0.789 p=0.0001) while both bone markers had a weak correlation with bone mass density of radius, lumbar spine and hip by DXA. (r=0.29 p=0.0001).

Analysis of polymorphism of the interleukin-6 gene in Thai subjects with osteoporosis.

Osteoporosis is the imbalance between bone formation by osteoblast and bone resorption by osteoclast. The genetic factors play an important role in determining bone mass and several genes probably act as regulators of this process. Interkeukin-6 (IL-6) is one of the candidate genes to regulate bone density, since IL-6 has some effect on stimulation of osteoclast resorption and has been implicated in the pathogenesis of bone loss associated with estrogen deficiency. We investigated the relationship between bone mineral density (BMD) and a polymorphic AT rich repeat in the 3' flank of the IL-6 gene in 272 Thai subjects. The subjects were classified into 3 groups i.e. normal healthy control (n=95), border-line (n=112) and osteoporotic patients (n=65). Five alleles different in sizes were identified (designated a, b, c, e and f). It was observed that c/c was the most common genotype in Thais (86.76%). The other genotype frequencies were 0.74, 3.31, 8.09, 0.74 and 0.37 for a/c, b/c, c/e, c/f and b/e genotypes, respectively. The common genotype was different from the Caucasians in a previous study. These frequencies were significantly different from the Caucasians (p<0.05). There was no significant relationship between 3' flanking AT repeat of the IL-6 genotypes and the BMD values of the distal forearm that were determined by One-way ANOVA (p>0.05). Additionally, the impact of the IL-6 genotypes on risk of osteoporosis was assessed by determination of the odds ratio. The c/e genotype may be a protective factor of osteoporosis. On the contrary, the b/c and c/c genotypes were considered to be risk factors of osteoporosis.

Efficacy of calcitriol to bone resorption and PTH level: clinical study.

Study of the effect of calcitriol (Rocaltrol) to bone markers and PTH level in 146 menopausal women. The result showed a dose of calcitriol 0.75 microgram/day for one month significantly decreased the level of PTH, bone marker for resorption and NMID osteocalcin 61.55, 69.92, 60.02 per cent respectively (p=0.000). The other group which took calcitriol 0.5 microgram/day had little change to such markers. The active form of vitamin D benefits bone health by enhancing osteocalcin formation, in addition vitamin D has moderate antiresorption and suppression of PTH secretion.

The parathyroid hormone level in Thai women.

Study of the correlation of parathyroid hormone (PTH) with age, radial bone mass and Nitrogenous mid fragment osteocalcin (NMID osteocalcin) in 226 menopausal women and 123 menstrual women. In menopausal women, aged between 50 and 69, the level of PTH did not increase with age (r=0.001, p=NS). Elderly women (n=123, age>70) showed a slight increase of PTH, 7.8 per cent compared to menstruating women. In elderly women (n=100, age>60) there was no weak correlation (r=0.11, p=0.0001) with bone mass of the distal end of the radius measured by Dual X-ray Absorptiometry (DXA) (Panasonic BDM-3) and no correlation between PTH and the resorptive bone marker, (betacrosslap) (r=0.11, n=122).

Safety and efficacy of meloxicam 7.5 mg in the treatment of osteoarthritis in Thai patients.

A prospective, open trial to evaluate the safety and efficacy of oral meloxicam 7.5 mg once daily over a period of 28 days in Thai patients with osteoarthritis was conducted in 3 major hospitals in Bangkok, Thailand. A total of 137 patients were enrolled and completed the study protocol. The mean age of the patients was 57.6 years and 88 per cent were female. Pain on movement and pain at rest evaluated after treatment by visual analog scale (VAS) were significantly improved with respect to the baseline status (p<0.001). The final efficacy was reported as satisfactory or good in 97 per cent and 94 per cent as determined by patients and physicians respectively. Patient status evaluated at the end of the study reported improvement of their arthritic condition in 84 per cent. Drug tolerability assessed by patients and physicians and was good or satisfactory in 99 per cent and 98 per cent. GI adverse event was reported in 8.8 per cent. Other adverse events were itching/rash in 2.0 per cent and headache/insomnia in 1.5 per cent of patients. No patients withdrew from the study due to adverse events. No GI bleeding or perforation were observed. No hospitalization was observed during the study. There was no significant change of blood chemistry and hematological profile between pre and post treatment examination. Results from this study suggest that oral meloxicam 7.5 mg for 28 days is a safe and effective treatment regimen with high GI tolerability profile for the treatment of osteoarthritis in Thai patients.

Serum dehydroepiandrosterone sulfate, testosterone, and biochemical markers of bone turnover in elderly Thai men.

The most abundant human steroid, dehydroepiandrosterone sulfate (DHEAS), may have a multitude of beneficial effects, but declines with age. It is unclear whether DHEAS deficiency is an important factor contributing to increased bone resorption and impaired bone formation or not that leads to their bone loss. Thus, we investigated serum DHEAS, testosterone, osteocalcin (N-MID osteocalcin) and C-terminal telopeptides (beta-CrossLaps) in 121 healthy Thai males without bone diseases. Thirty-nine males (mean age 31.5 +/- 8.2, range 23-42 years) were recruited as the normal adult group and 82 males (mean age 61.2 +/- 7.0, range 52-77 years) were assigned as the elderly group. DHEAS levels were higher in the adult group compared with the elderly subjects (296.8 +/- 93.4 vs 172.6 +/- 99.8 microg/dL, p < 0.0001). Serum osteocalcin concentrations were also higher in the adult group compared with the elderly males (27.9 +/- 11.1 vs 23.2 +/- 7.9 ng/ml, p = 0.0091). However, serum testosterone and C-terminal telopeptides levels were not significantly different between the two groups. We concluded that low DHEAS concentrations are commonly encountered in elderly males and may relate to low osteocalcin levels due to the osteoblast stimulation effects of DHEAS. These findings may be implicated in the treatment of osteoporosis in elderly men by using DHEAS.

Treatment of painful osteoarthritis of the knee with hyaluronic acid. Results of a multicenter Asian study.

Hyaluronic acid is a component of synovial fluid, in osteoarthritis (OA) and shows a change of property of hyaluronic acid especially its viscoelasticity causing degradation of the cartilage. Injection of hyaluronic acid into OA of the knee (Hyalgan 2 ml/wk for 4 doses) in international multicentres gave dramatic responses: decreased pain, increased mobility of the joint after 49 days of injections compared to a placebo (2 ml of normal saline) p<0.01.

The use of historical and anthropometric data as risk factors for screening of low mBMD & MCI.

To evaluate the risk factors which affect bone loss in screening for osteoporosis, interview of anamnestic data (age, marriage status, pregnancies, menopausal age, intake of calcium, vegetables, protein and coffee, excessive use of alcohol and smoking, sedentary habits, family history), medical data, surgical data, followed by measurement of anthropometric variables [weight, height, antero-posterior (AP) thickness at xiphoid level], blood examination (calcium, inorganic phosphorus, alkaline phosphatase), both postero-anterior (PA) hands and lateral thoraco-lumbar radiography were done in 1,182 normal volunteers aged 17-83. From PA hands radiographs, metacarpal bone mineral density (mBMD) and metacarpal index (MCI) were measured by computed X-ray densitometry (CXD) (Bonalyzer, Teijin Ltd., Tokyo). The results showed that the mean of menopausal age in Thai females was 48.86 +/- 3.09 years ranging from 39 to 55 years. The average number of children in their family was 2.10. Correlation among anthropometric variables, AP thickness was positive linear correlation to weight/height ratio (r = 0.7878, p-value < 0.005). Weight, AP thickness and body mass index (BMI) significantly increased with aging (r = 0.2456, 0.4489 and 0.3484, p-value < 0.005, 0.001 and < 0.005), but decreased with height (r = -0.1030, p-value = 0.001). Lower mBMD and MCI were associated with increased age, married female, increased pregnancies, increased AP thickness, decreased vegetable intake, increased protein intake and increased years after menopause. From a multiple regression analysis, the significant factors that can predict the MCI were years after menopause, sex, daily vegetable intake and hormonal replacement. The incidence rate of high risk of developing osteoporosis in females, no vegetable intake and no hormonal replacement subjects occurred 7.50, 2.22 and 2.63 times greater than in males, vegetable intake and hormonal replacement subjects, respectively. In postmenopausal women since 1-2, 3-5, 6-10, 11-15 and > 15 years, the incidence rate were 5.24, 14.51, 17.01, 20.86 and 29.76 times greater than the rate of premenopausal women. Concerning perimenopausal women, only 2 of all factors influenced the measured mBMD and MCI. The incidence rate of high risk of developing osteoporosis in women who intake protein > 30 g/d and intake medicine (corticosteroid) was 2.96 and 6.16 times greater than < 30 g/d protein intake and no medicine intake subjects.

Computed X-ray densitometry measurement of mBMD & MCI in normal Thai and osteoporotic patients.

To establish the reference values of age-related change of metacarpal bone mineral density (mBMD) and metacarpal index (MCI) in screening for osteoporosis, both postero-anterior (PA) hands and lateral thoraco-lumbar radiography were done on 1,182 normal volunteers aged 17-83. From PA hands radiographs, mBMD and MCI were measured by computed X-ray densitometry (CXD) (Bonalyzer, Teijin Ltd., Tokyo). Exclusion of the surgical menopause condition and the causes of affected bone loss, the results show that mean mBMD and MCI in various age groups were significantly different (p-value < 0.005 for both) in females. Both values increased gradually from age under 20 and peaked in the 30-39 years age group, then decreased gradually until age 50 and decreased markedly after age 50. The yearly rate of bone loss from the peak density detected by mBMD and MCI was 1.3 per cent and 1.6 per cent between aged 50-59, 1.6 per cent and 2.7 per cent in subjects aged 60-69, 1.3 per cent and 3.2 per cent in those aged 70-79. However, mBMD and MCI in males did not show a downward trend with age. It indicated that a screening program for early prevention of osteoporosis may be necessary only in females before, during and after menopause. Because 92.3 per cent of 39 osteoporotic subjects had abnormal CXD measurements lower than -2 standard deviations (SD) limit of mean mBMD in young healthy women (aged 20-40 years), this value appeared to constitute a satisfactory definition of "high risk of developing osteoporosis". The incidence rate of high risk of developing osteoporosis was 3.03 per cent in a normal young population, while the risk rate occurred 4.76, 13.14, 34.28, 47.30 and 47.00 per cent in subjects aged 40-49, 50-59, 60-69, 70-79 and > 80, respectively. Results confirmed the necessity of early prevention of osteoporosis in postmenopausal women. These measurements may be appropriate for mass screening to separate patients who have a greater risk for development of osteoporosis from those at lesser risk.