Estimation of Osteoblastic Functions by Biological Bone Markers.

The purpose of this study is to identify the lowest value ofNMID osteocalcin and PINP when CTx is below or equal to 0.10 ng/ml at which neither bone formation nor bone resorption occurs. This may be harmful to bone texture. The 223 cases of CTx equal or below 0.100 ng/ml of CTx were enrolled. They consisted of 42 cases or 18.83% of menopausal women, 110 cases or 49.32% ofpost anti-resorptive therapy, 22 cases or 9.8% elderly and 49 cases or 21.97% unknown causes. The results show PINP = 15.88 ng/ml and NMID osteocalcin = 10.81 ng/ml. We used them as a cut value for diagnosis of bone condition. The benefits of this study: helping the physician in the treatment of bone diseases, osteoporosis in cases of over treatment, when the value of CTx is below or above 0.1 ng/ml or 0.01-0.099 ng/ml; when there is no bone resorption and osteoblastic function is poor if the values of NMID osteocalcin or PINP are still equal to 10.81, 15.88 ng/ml at any level of BetacrossLap, respectively.

Efficacy of Bisphosphonates Evaluated by Biological Bone Markers.

This research aimed to study the benefits of bone markers on bisphosphonate, alendronate plus (vitamin D3 2800IU) administered once a week as a model especially regarding BetacrossLap, CTx. The enrolled cases were 306 (female = 282, male = 24) with high CTx (≥ 0.300 ng/ml). The exclusion criteria were diabetes, abnormal renal or liver profiles, recent fractures and medication 1 month before the study. The duration of observation was 3 months for making decision on treatment. The bloodfor bone markers were checked at thefirst and third months. It was found that 10 percent of alendronate intake showed no response, i.e. neither decrease nor increase in CTx and 16.1 percent of cases showed strong bone suppression, i.e. high anti-resorption which the value of CTx below 0.100 ng/ ml after 3 months of the treatment. This bad condition may induce bone crack or stress fracture in the long run. It was also found 83.9 percent of cases presented good responses with the value ofCTx at 0.100-0.299 ng/ml after 3 months. These cases can be continuing bisphosphonate until good satisfaction takes place. The benefits of bone markers help the physicians' decision either to stop or continue the treatment. For the no response group, the bone markers (CTx) will save the cost oftreatment. When the anti-resorption is marked (CTx < 0.100 ng/ ml), the physicians can stop the treatment before unwanted effects occur. The bone markers shorten the timefor producing the treatment results and indicting whether the bisphosphonates have been properly used. The bone markers, formative marker, PINP showed a decrease in bone formation after 3 months; PINP = 38.51%. This is a good lesson to be learned, that boneformation hardly ever occurs especially primary boneformation in cases where bisphosphonates is being taking. This study manifested the benefits of biological markers with quick response that can help the physicians treat the patients properly, save time and the cost of medication.

Study of the Safe Dosage of Ergocalciferol.

Vitamin D2 or ergocalciferol can replace vitamin D3, but its dosage must be a higher international unit: one unit of vitamin D3 is equal to 4 units ofvitamin D2. A proper interval of administration should take 200,000 IUper day. The 123 cases enrolled for study, every case had blood levels of 25 (OH) D and blood calcium checked before intake of vitamin D2 followed by a second check after 2 months. The means of before-intake group was 31.92 ng/ml and after-intake group was 48.62 ng/ml; the pair sample mean was 0.001. We found the level of 25 (OH) D was greater than 70 ng/ml (max = 90), 3.2 percent. Twelve cases showed no response, 9.6 percent. No cases of hypercalcemia or allergic phenomenon were noted. Before the study, we tried a random dosage of 200,000 IU per week and found the pair mean showed nothing significant (p = 0.052). In practice, the dosage of 200,000 IU of vitamin D2 is suitable for treatment of vitamin D deficiency, but for long-term treatment, dosage should be adjusted by monitoring the levels of 25 (OH) D from time to time.

The Intriguing Correlation between Undercarboxylated Osteocalcin and Vitamin D.

Osteocalcin (OC) or bone Gla protein (BGP), a bone specific protein, is one of circulating biomarkers that can be used to determine the quality of bone tissues. It is synthesized by the osteoblast and the odontocyte. The process of OC production requires two types ofvitamin: vitamin D and vitamin K. Vitamin D is requiredfor the production of immature OC or undercarboxylated OC (UcOC) whereas vitamin K is requiredfor the transformation of UcOC to mature OC. In the past, several researchers believed that UcOC was the sensitive marker to determine vitamin K status. In fact, the level of UcOC also depends on vitamin D. This study aims to know the correlation between the levels ofvitamin D and UcOC. The collected data of UcOC and vitamin D levels from 95 healthy volunteers were analyzed. The finding was that there was a weak correlation between UcOC and vitamin D (r = 0.238; p = 0.020) together with UcOC and reciprocal ofvitamin D (r = 0.267; p = 0.009). From this correlation, the serum level of UcOC may be not the real marker for vitamin K.

Effects of Short-Term Vitamin D Supplementation on Musculoskeletal and Body Balance for Prevention of Falling in Postmenopausal Women.

OBJECTIVE: The objective of this research was to examine the effects of the short-duration (4 weeks) vitamin D supplementation on biochemical bone markers, muscle strength and balance of the postmenopausal females. MATERIAL AND METHOD: The participants consisted of 52 female participants from Chulalongkorn University, aged between 45-55 years old. They were divided into two groups: 26 females in the vitamin D supplementation (VID) and 26 females in the control group (CON) by the simple random sampling method. The experimental group received 20,000 IU of vitamin D2 per week, for a period of 4 weeks. The control group did not receive vitamin D2. The collected data before and after the experiment were the results of the physiology test, the biochemical bone markers, the muscle strength and the balance ability. The collected data were compared and analyzed by the mean and standard deviation. The differences of the tests are statistically significant at the 0.05 level. RESULTS: After the 4-week experiment, the vitamin D2 supplementation group had significantly improved balance ability on normal stability surfaces when being compared with the pretest and the control group (p < 0.05). CONCLUSION: A short-term vitamin D2 supplementation had positive effect on balance. This is, therefore, a good alternative for postmenopausal people and may reduce the risks of falling in women in particular.

Effects of Aerobic Step Combined with Resistance Training on Biochemical Bone Markers, Health-Related Physical Fitness and Balance in Working Women.

The objectives of this research were to develop an aerobic step combined with resistance training exercise program, and to compare the effects of A) aerobic step exercise training (STE), B) resistance aerobic exercise training (RES), C) a combined aerobic step with resistance exercise training (COM) on the health-related fitness, balance, and biochemical bone markers. Sixty participants were working female volunteers at the age of 35-45. They were divided into 4 groups by simple random sampling method. Fifteen of the participants were in the STE group, 14 in the RES group, 15 in the COM group, and 16 in the control group (CON). The STE, RES and COM exercise training programs were designed to yield the same intensity and achieve the same range of heart rate during each stage of the program. During the training, music was used to set the tempo of the workouts. At the 8th week, it was found that resting heart rate and systolic blood pressure significantly-increased only in the STE and COM groups. After 16 weeks, the experiment results showed the significant improvement in the COM and STE groups of exercise training for ß-CrossLaps, P1NP NMID Osteocalcin and bone formation (PINP/ß-CrossLaps x0.31) but not in the RES group. For balance ability, the COM group showed significantly greater change than the RES group after the training intervention (p < 0.05). It can thus be concluded that the STE and COM training were effective in improving bone formation (PINP/ß-CrossLaps x 0.31) but not in the RES group. For balance ability, the COM group showed more significant change than the RES group. Therefore, this is not only a good exercise choice for the working-age people but also it can help reduce the risks of osteoporosis and falling in women in particular.

A Comparison between the Effects of Aerobic Dance Training on Mini-Trampoline and Hard Wooden Surface on Bone Resorption, Health-Related Physical Fitness, Balance, and Foot Plantar Pressure in Thai Working Women.

OBJECTIVE: To compare the effects of aerobic dance training on mini-trampoline and hard wooden surface on bone resorption, health-related physical fitness, balance, and foot plantar pressure in Thai working women. MATERIAL AND METHOD: Sixty-three volunteered females aged 35-45 years old participated in the study and were divided into 3 groups: A) aerobic dance on mini-trampoline (21 females), B) aerobic dance on hard wooden surface (21 females), and C) control group (21 females). All subjects in the aerobic dance groups wore heart rate monitors during exercise. Aerobic dance worked out 3 times a week, 40 minutes a day for 12 weeks. The intensity was set at 60-80% of the maximum heart rate. The control group engaged in routine physical activity. The collected data were bone formation (N-terminal propeptine of procollagen type I: P1NP) bone resorption (Telopeptide cross linked: ß-CrossLaps) health-related physical fitness, balance, and foot plantar pressure. The obtained data from pre- and post trainings were compared and analyzed by paired samples t-test and one way analysis of covariance. The significant difference was at 0.05 level. RESULTS: After the 12-week training, the biochemical bone markers of both mini-trampoline and hard wooden surface aerobic dance training subjects decreased in bone resorption (ß-CrossLaps) but increased in boneformation (P1NP). Health-related physical fitness, balance, and foot plantar pressure were not only better when comparing to the pre-test result but also significantly different when comparing to the control group (p < 0.05). The aerobic dance on mini-trampoline showed that leg muscular strength, balance and foot plantar pressure were significantly better than the aerobic dance on hard wooden surface (p < 0.05). CONCLUSION: The aerobic dance on mini-trampoline and hard wooden surface had positive effects on biochemical bone markers. However, the aerobic dance on mini-trampoline had more leg muscular strength and balance including less foot plantar pressure. It is considered to be an appropriate exercise programs in working women.

Effects of Circuit Aerobic Step Exercise Program on Musculoskeletal for Prevention of Falling and Enhancement of Postural Balance in Postmenopausal Women.

OBJECTIVE: The objective of this research was to develop a circuit aerobic step exercise program and to examine the effects of the circuit aerobic step exercise program on bone formation, bone resorption, muscle strength and body balance of the postmenopausal females. MATERIAL AND METHOD: The samples consisted of 52 female participants from Chulalongkorn University, aged between 45-55 years old. The subjects were divided into two groups: 26 females in the circuit aerobic step exercise group (CASE) and 26 females in the control group (CON) by the simple random sampling method. The experimental group participated in the aerobic step exercise program while wearing heart rate monitors. The exercise speed was determined by the rhythm of the music. The experimental group completed two circuits of aerobic step exercise at 6 stations, 3 times per week, for a period of 4 weeks. The intensity is 55-75% of a maximum heart rate. The control group did not participate in the circuit aerobic step exercise program. The collected data of the before and after experiment were the results of physiology test, biochemical bone markers, muscle strength and balance ability. The collected data were compared and analyzed by the mean and standard deviation. The differences of the tests were statistically significant at the 0.05 level. RESULTS: After the 4-week experiment training, the circuit aerobic step exercise group had significantly decreased in resting heart rate and bone resorption (p < 0.05). Muscle strength and balance on normal stability surfaces improved significantly only in the circuit aerobic step exercise group when being compared with the pretest and the control group (p < 0.05). CONCLUSION: The circuit aerobic step exercise had positive effect on bon eformation, muscle strength and body balance. This, therefore, is a good exercise choice for postmenopausal people and can help reduce the risks of falling especially in postmenopausal women.

Parathyroid hormone enhances osteoblast differentiation from human skin derived precursor cells in vitro.

Parathyroid hormone (PTH), a new effective treatment for osteoporosis patients which promotes the anabolic effect in vivo, can enhance the differentiation of osteoblasts derived from the human skin-derived precursor cells (hSKPs) in vitro culture. This research investigated the effects of PTH by studying the gene expressions and other markers of osteoblast differentiation along with the induction of hSKPs to osteoblast in two experiment groups, i.e. the osteogenic induction medium (OM) only and the OM plus PTH (OM + PTH). The results of each type were compared between these two groups. Both groups expressed the Cbfa1 gene, a regulator of osteoblasts and also one of the most osteoblast specific genes. The findings were that the OM + PTH group showed more intense alkaline phosphatase staining than the other. The gene expressions of protein showing the mature osteoblasts like osteocalcin (OCN) and bone sialoprotein (BSP) in the OM + PTH group expressed higher and faster (Day 14) than the OM group. Moreover, the gene expression of osteoprotegerin (OPG) possessing the protein produced by the mature osteoblasts showed a higher level in the OM + PTH group on the same day as OCN and BSP occurred. This protein performs a function in inhibiting osteoclast maturation. The present study found that PTH enhanced the differentiation of osteoblasts derived from hSKPs by promoting the maturation of osteoblasts in vitro. It possibly concerns with the anabolic effect of PTH in a treatment for osteoporosis patients. Additionally, hSKPs are the interesting sources for osteoporosis treatments when combining with PTH.

Recommended dose of alfacacidol for osteoporosis.

The present study aims to investigate a proper dose of alfacalcidol by using the parathyroid level as a marker due to the end product of alfacalcidol is calcitriol which has a property of suppression secretion of parathyroid glands. The research enrolled 259 volunteers which were divided into 2 groups. Each group took the elemental calcium 800 milligram plus alfacalcidol at the different doses. Group (A) received alfacalcidol 1.0 microgram/day and Group (B) had alfacalcidol 1.5 micrograms/day for 3 months. Group (A) could not suppress the secretion of PTH compared with Group (B) of which the PTH level was decreased significantly (p = 0.047). Alfacalcidol in both groups can not decrease the bone resorption monitored by using the bone resorption marker, BetacrossLaps or bCTx.

Effects of the circuit box jumping on bone resorption, health-related to physical fitness and balance in the premenopausal women.

The purpose of this research is to develop a circuit box jumping exercise program and to examine the effects of the circuit box jumping exercise program on bone formation, bone resorption, health related to physical fitness and balance of the premenopausal females. The samples consisted of 57 female volunteers from Chulalongkorn University, aged between 35-45. The subjects were divided into two groups: 28 females in the experimental group and 29 females in the control group by the simple random sampling method. The experimental group participated in the circuit box jumping exercise program while wearing heart rate monitors. The exercise speed was determined by the rhythm of the music. The experimental group completed two circuits of jumping at 6 stations with 10 jumps per station three times per week, for a period of twelve weeks. Each jumping box at Station 1 and 4 was 10 cm. high; the boxes at Station 2 and 5 were 15 cm. high; and at Station 3 and 6, the boxes were 20 cm. in height. The intensity is 60%-80% of a maximum heart rate. The control group did not participate in the circuit box jumping exercise program. The collected data before and after the experiment were the results of the physiology test, the biochemical bone markers, the health related physical fitness and the balance ability. The collected data were compared and analyzed by the mean and standard deviation. The differences of the tests are statistically significant at the .05 level. The results of the present study are as follows; 1. After the 12-week experiment training, the findings indicated that the mean scores on bone resorption (beta-Crosslaps) of the experimental group and the control group were significantly different at 0.05 level. In addition, the findings showed that the percentage changes on bone resorption (beta-Crosslaps) variance of the experiment group reduced by -25.6528%, while that of the control group reduced by -0.5933%. Bone formation (PINP/beta-Crosslaps) in the circuit box jumping subjects was significantly higher after the training intervention (p < 0.05). 2. The general physiological data in the circuit box jumping subjects after the training intervention was significantly lower in weight, resting heart rate and systolic blood pressure (p < 0.05). 3. The health-related to physical fitness in the circuit box jumping subjects after the training intervention was significantly lower in waist/hip ratio, body fat and fat in percent while skeleton muscle mass, leg strength, flexibility and VO2max were significantly higher after the training intervention (p < 0.05). 4. The balance in the circuit box jumping subjects after the training intervention was significantly better after the training intervention (p < 0.05). The circuit box jumping training has the positive effects on slowing down the bone resorption and consequently the bone formation increased. It can be concluded that the circuit box jumping training reduces some risks of osteoporosis in the premenopausal women. Additionally, it promotes the better health-related to physical fitness and balance.

Experience of application: blood screening and bone turnover markers for prevention of unwanted effects and early outcomes of teriparatide.

This clinical study aimed to provide awareness of the teriparatide injection and also prevention of unwanted events. The 72 cases aged between 52-69 with the inclusion criteria: back pain proved by the x-ray with one or more collapsed spines, no underlying diseases and no history of bone tumor, hyperparathyroid, hypercalcemia. The blood screening for renal, liver profiles, uric acid, mineral profile and bone turnover markers (bCTx, PINP) are used as 6-month monitor. The results showed that the common unwanted effects were hypercalcemia, hyperuricemia, hypomagnesia: 5.5%, 54.56% and 43% respectively at the first month of the therapy. At the end of 6th month, these conditions occurred 1.38%, 8.77% and 5.5% respectively. The bone turnover markers, PINP, was a quick response in the first month, the PINP was double increased then triple increased at the end of the 6th month (p = 0.001). Teriparatide did not disturb the activity of parathyroid glands because the PTH was within the normal limit during the treatment (p = 0.001). The blood screening monitor was useful for preventing the unwanted effects and the bone turnover markers, PINP was beneficial for evaluation of Teriparatide efficacy in short outcomes leading to physicians and patients' confidence.

The action of Strontium ranelate: myth or reality.

The present study aimed to show whether the Strontium ranelate was the dual action possessing either antiresorptive or formative properties. This retrograded study included 56 postmenopausal women using the biological bone turnover markers as an evaluation. The antiresorptive property described by the mean value of Beta-crossLap or bCTx before taking 2 grams of Strontium ranelate per day was 0.377 ng/ml compared with the mean of CTx after the 3-month treatment which was 0.409 (p = 0.083) ng/ml. The result indicated that this agent could not suppress the bone resorption, otherwise Strontium ranelate was not able to control the progress of bone resorption. It was found that 67.92 per cent showed the uncontrollable resorption. In addition, the bone formation monitored by PINP was diminished 34.54% and only 60% of the bone formation values was little increased but still below normal (44.5 ng/ml) while 1.8% was no response. The present study displayed that the Strontium ranelate was neither antiresorptive nor formative actions and it was certainly not a dual action via the method of biological bone turnover markers.

The bone turnover markers in healthy Thai adults as the standard values.

The present study of the bone markers in the healthy Thai females and males enrolled 588 females and 53 males with age range from 25 to 42 years. The potential modification of variations was controlled. The bone resorptive markers, betaCTx, of females and males were 0.3 +/- 0.169, 0.412 +/- 0.191 ng/ml respectively. The bone formation markers, PINP, of females and males were 44.5 +/- 19.92, 58.1 +/- 37.7 ng/ml respectively. These markers could be recognized as the standard values for comparison.

Calcium supplement: humanity's double-edged sword.

The principle aim of the present study is to investigate the dark side of calcium, pollutions in calcium preparation especially lead (Pb), mercury (Hg) and cadmium (Cd). The collected samples were the different calcium salts in the market and 18 preparations which were classified into 3 groups: Calcium carbonate salts, Chelated calcium and natural-raw calcium. All samples were analyzed for lead, cadmium and mercury by inductively Coupled Plasma Mass Spectrometry (ICP-MS) technique, in house method based on AOAC (2005) 999.10 by ICP-MS. The calcium carbonate and the natural-raw calcium in every sample contained lead at 0.023-0.407 mg/kg of calcium powder. Meanwhile, the natural-raw calcium such as oyster, coral and animal bone showed amount of lead at 0.106-0.384 mg/kg with small amounts of mercury and cadmium. The chelated calcium such as calcium gluconate, calcium lactate and calcium citrate are free of lead.

A study of correlation of osteoblasts from peripheral blood with related bone turnover markers.

The bone remodeling process called osteoblasts has an important role in bone formation working together with osteoclasts of which the cells are responsible for bone resorption. In addition, these bone turnover markers are used to follow-up the conditions of bone remodeling in the patients. Recently, osteoblastic lineage cells have been found that they exist in the human peripheral blood. However there has been no report about the amount of circulating osteoblastic lineage cells that have the relationship with the samples of bone turnover markers showing the bone remodeling condition. In the present study, circulating osteoblasts were quantified in 43 subjects aged between 25-90 years. They were classified by age into 3 groups: A) lower than 60 years old (n = 9), B) from 60 to 79 years old (n = 22) and C) equal and over 80 years old (n = 12). All were studied by the flow cytometry method using an antibody to osteocalcin and bone turnover markers beta-CrossLab (betaCTx), PINP and NMID. These markers including parathyroid hormone were analyzed. The result showed the best positive correlation between the percentage of circulating osteoblasts and bone turnover markers of the equal and over 80-year-old group. While another result exhibited the negative correlation of circulating osteocalcin positive cells with the bone turnover markers in the group of lower than 60 years old. As circulating osteoblasts had the correlation with bone turnover markers in the group aged 80 years old, this could be used as the markers to follow up the bone turnover situation of the patients in this age group. However, this is a pilot study. Further analysis of more amounts of subjects should be done for a better result.

Study of validity of pyridinoline and correlation of pyridinoline and beta crosslap in postmenopausal women.

This research studied the validity and correlation of beta-CTx (Betacrosslap) and Pyridinoline (PYD) in 71 cases of postmenopausal Thai women who attended at the osteoporosis clinic. The validity consisted of sensitivity, specificity and accuracy of PYD. They were 53.44, 84.6 and 59.15% respectively. So, the validity of pyridinoline test was rather poor and the correlation between betacrosslap and pyridinoline was weak (r = 0.123, p = 0.0001) which was not significant in practice. In conclusion, the pyridinoline test was not proper for bone resorption even pyridinoline was abundant in bone.

Osteoblastic functions: a lesson from biochemical bone markers.

The present study showed the lowest values of bone markers from osteoblast, NMID osteocalcin, 10.81 +/- 3.9 ng/ ml and PINP 15.88 +/- 7.09 ng/ml at lowest level of osteoclast, betaCTx, 0.066 + 0.22 ng/ml should be the cut value for osteoblastic function. At this level betaCTx, had no correlation with PINP (r = 0.198, p = 0.003) or NMID osteocalcin (r = 0.035, p = 0.606) compared to the normal value of the control group and the correlation (r) between betaCTx and NMID osteocalcin, betaCTx and PINP, which were 0.757 and 0.752 (p = 0.001) respectively and recognized as normal bone turnover with coupling effect. So, bone markers of osteoblast at the lowest value of betaCTx (0.066 ng/ml) with NMID osteocalcin, 10.81 +/- 3.9 ng/ml and PINP 15.887.09 ng/ml may be the cut value of osteoblast reflecting poor functions. The benefit of identifying the cut values of osteoblast will help in making decisions in osteoporotic management.

The reality of osteocalcin as a marker of vitamin K2.

The present study showed the correlation between undercarboxylated osteocalcin and vitamin D had a role in production of the undercarboxylated osteocalcin, when the amount of vitamin D 25 (OH) D, (below 30 ng/ml) was decreased, the linear correlation (r) between the vitamin D and undercarboxylated osteocalcin were also decreased r = 0.032 when the level of vitamin D was risen, the linear correlation was 0.274,unfortunately the study-population had little group of the normal level of vitamin D due to most of them were vitamin D insufficiency so the authors could not show the more value of 'r'. However, the present study confirmed that the role of vitamin D information of undercarboxylated osteocalcin (UcOC) which we recognized the UcOC at the low level of vitamin D will misinterpretation of the level of vitamin K2.