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EZorb Calcium®   Calcium Aspartate Anhydrous

Treatment of Osteoporosis


Effects of Calcium Aspartate Anhydrous on Treatment of Osteoporosis

J.F. Tang, Ph.D., Haitian Liu, Ph.D., Qiang Wang, Ph.D., X.S.Bai, Ph.D., Tianlin Lou, Ph.D., Tongge Yang, Ph.D., Haihuan Song, M.D., Qing Zhu, M.D., Q.C. Guo, M.D., Mingkun Zhao, M.D., Baoguo Chen, M.D., Yueshan Xie, M.D., Jiawen Hu, M.D., Haiying Zhou, M.D., Lei Song, M.D., Jun Chen, M.D., and Xiaoming Li, M.D.

ABSTRACT

Background Osteoporosis is a common metabolic bone disease. We conducted a multi-center, doubleplacebo, double-blind study to verify the effects of calcium aspartate anhydrous on osteoporosis.

Methods 1,306 patients with an initial t-score of -1.5 or lower were randomly assigned to receive
calcium aspartate anhydrous (CalAA, 520mg elemental per day) and a placebo, or calcium citrate (1500 mg elemental per day) and vitamin D (1000 IU per day), or two placebos.

Results At 3 months, the bone mineral density (BMD) at the lumbar spine had increased by a mean of 4.07% in the CalAA group, 0.64 percent in the calcium citrate group and there was no significant change in the double-placebo group. The BMD of the total hip had increased by a mean of 3.37 percent in the CalAA group. No significant change was detected in the calcium citrate group or the double-placebo group. At 12 months, lumbar spine BMD had increased by a mean of 5.66 percent in the CalAA group, while the calcium citrate group and the double-placebo group saw decline of 0.51% and 0.75% respectively. Total hip BMD had increased by a mean of 4.11 percent in the CalAA group while there was no significant change in the calcium citrate group. Total hip BMD declined by a mean of 1.17% in the double-placebo group.

Conclusions Calcium aspartate anhydrous increases bone mineral density significantly. Calcium citrate plus vitamin D may help slow down bone loss at the hip.

The exact cause of primary osteoporosis is not clear at present, but it is generally the co-interaction result of a number of factors and links. Most believe that the occurrence of osteoporosis is associated with various factors such as increased age, decreased hormone level, and calcium dysbolism, etc. As for women, particularly for menopausal women, many researchers believe that the occurrence of osteoporosis is closely related to decreased estrogen level and calcium dysbolism. The occurrence of osteoporosis in aged men can also be attributed to multiple factors. Androgens of aged men participate in the process of bone metabolism and play important roles in bone formation and maintenance. In addition, increased secretion of parathormone in the aged men reduces the bone formation but enhances the bone resorption. Kidney degeneration in aged men reduces the activity of hydroxylase, which in turn, decreases calcium absorption in the small intestine, causing negative calcium balance and loss of bone matrix. Attempts have been made to treat osteoporosis with a variety of pharmacological agents,
such as estrogens and bisphosphonates. Evidence shows that those therapies have limited success in osteoporosis treatment. Therefore, a more effective method of preventing and treating osteoporosis is desirable.

METHODS

Study Design
In this one-year, multi-center, double-placebo, double-blind study, patients with t-score under -1.5, were randomly assigned to three groups. Group I receives CalAA (4 g per day, 520 mg elemental) and a placebo matching Vitamin D. Group II receives calcium citrate (1,500 mg elemental per day) and Vitamin D (1000 IU per day). Group III was given one placebo matching calcium, and another placebo matching Vitamin D.

Study Profile
A total of 1,306 patients were eligible. The criteria for exclusion were hormone-replacement therapy initiated within the previous year, or the use of bisphosphonates or calcitonin therapy.

Twenty-one patients withdrew before the 3-month visit, and thirty-four withdrew before the 12-month visit. The rate of retention for 12 months was 96.3% in the CalAA group, 95.4% in the calcium citrate group and 95.6% in the double-placebo group. Figure.1 gives details of the study profile.

Bone Density Measurements
Baseline measurements of bone mineral density were obtained immediately after signing of the consent forms. The measurement of bone density was repeated at 3 and 12 months. The primary efficacy endpoints were the percent changes in the bone mineral density of the lumbar spine and the total hip at 3 and 12 months.

Bone density was measured with the use of a dual-energy x-ray absorptiometry (Hologic QDR-4500), and was expressed in grams per square centimeter.

Statistical Analysis
Statistical models were designed to detect differences between the groups in the BMD percentage
change from baseline to 3 months and from baseline to 12 months in the spine, the femoral neck, and the hip, with a two-tailed P value of 0.05 and 95% confidence intervals. The primary analyses compared Group I and Group II at 3 months and 12 months. Secondary analyses compared Group I and Group III, Group II and Group III, at 12 months.

RESULTS

Study Population
The groups did not differ significantly in terms of age, sex, or baseline bone density (Figure 1 and Table 1).

Figure 1. Study Profile.

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Bone Mineral Density Change

At 3 months, the bone density of the spine had increased by 4.07% in Group I (95% confidence interval, 2.03-6.11) and by 0.64% in Group II (95% confidence interval, -0.54-1.02). The bone density at the femoral neck increased by 2.54% in Group I (95% confidence interval, 1.73-3.22) and by 0.80% in Group II (95% confidence interval, -0.32-1.13). The bone density of the total hip increased by 3.37% in Group I (95% confidence interval, 2.34-3.98) and decreased by 0.58% in Group II (95 percent confidence interval, -1.24-0.25).

Analyses showed there was significant difference between Group I and Group II in BMD percentage change. The difference between the changes in the two groups was 3.43% for the change at the spine (95% confidence interval, 1.37-4.94; P=0.01), 1.74% for the change at the femoral neck (95 percent confidence interval, 0.34 to 3.36; P=0.04), and 3.95% for the change at the total hip (95 percent confidence interval, 1.02 to 4.71; P=0.03).

At 12 months, the BMD of the spine had increased by 5.66% in Group I (95% confidence interval, 2.12-7.23) and decreased by 0.51% in Group II (95% confidence interval, -0.54-1.02). The bone density at the femoral neck increased by 3.49% in Group I (95% confidence interval, 1.73-5.22) and by 0.03% in Group II (95% confidence interval, -0.62-0.93). The bone density of the total hip increased by 4.11% in Group I (95% confidence interval, 2.34-5.98) and decreased by 0.07% in Group II (95 percent confidence interval, -1.01-0.98). Difference between Group I and Group II in BMD percentage change is significant at 12 months. The difference between the changes in the two groups was 6.17% for the change at the spine (95% confidence interval, 4.02-8.94; P=0.003), 3.46% for the change at the femoral neck (95 percent confidence interval, 1.27 to 5.14; P=0.02), and 4.18% for the change at the total hip (95 percent confidence interval, 2.23 to 6.57; P=0.01).

Changes to BMD Picture

Secondary analyses revealed that the difference in BMD change in the spine is significant between Group I and Group III (6.41%; 95 percent confidence interval, 4.03-8.12; P=0.001). But there was no significant difference between Group II and Group III (0.25%; 95 percent onfidence interval, -1.05 to 1.16; P=0.35). For the femoral neck, the estimated difference between Group I and Group III was 3.96% (95 percent confidence interval, 2.10 to 6.73; P=0.003), and the estimated difference between Group II and Group III was 0.50% (95 percent confidence interval, -0.91 to 1.06; P=0.05). For the total hip, the estimated difference between Group I and Group III was 5.28% (95 percent confidence interval, 3.48 to 7.31; P=0.001), and the estimated difference between Group II and Group III was 1.24% (95 percent confidence interval, -0.13-2.56; P=0.04).

BMD changes by age in Group I at 3 months and 12 months are reported in Table 4 and Table 5 respectively. Figure 2 shows that the estimated BMD percentage increase declines by age. This phenomenon is consistent at 3 months and 12 months.

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Changtes to BMD 12 Picture
BMD Changes by age Picture

Conclusion
We conclude that calcium aspartate anhydrous increases bone mineral density significantly in 3-12 months. Calcium citrate plus vitamin D may help slow down bone loss at the hip.


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