Oss-Pro CLINICAL TRIALS REVEAL OHC EFFICACY On a gram-per-gram basis ossein hydroxyapatite complex (OHC) repeatedly has proved to be superior to other sources of calcium. Long-term clinical trials with OHC continue to yield superior clinical results. Here are some examples:

—2011—Comparison of the effects of ossein-hydroxyapatite complex and calcium carbonate on bone metabolism in women with senile osteoporosis: a randomized, open-label, parallel-group, controlled, prospective study.2

RESULTS: In this group of women with active osteoporosis, OHC significantly reduced bone loss in the lumbar spine and significantly increased BMD in the femoral neck between baseline and year three.

CONCLUSION: OHC had a greater anabolic effect on bone than did calcium carbonate.

—20093—Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis.

RESULTS: Of the 18 controlled trials initially identified, six were included in the meta-analysis. There was no significant heterogeneity among the included trials. The percent change in BMD significantly favored the OHC group (1.02 percent [95 percent CI, 0.63.1.41], P < 0.00001). These results were confirmed in the sensitivity analysis.

CONCLUSION: OHC is significantly more effective in preventing bone loss than is calcium carbonate.

—20074—Prevention of osteoporosis: four-year follow-up of a cohort of postmenopausal women treated with an ossein-hydroxyapatite compound.

RESULTS: A progressive and statistically significant increase in BMD was observed in trabecular and total T- and Z-score mean values.

CONCLUSION: Ossein-hydroxyapatite compound could be an effective and safe agent for the prevention of bone loss in postmenopausal osteopenic women, with significant increases in BMD being observed in this group of patients.

—20045—Comparison of the effects of two different types of calcium supplementation on markers of bone metabolism in a postmenopausal osteopenic population with low calcium intake: a double-blind placebo-controlled trial.

RESULTS: The study compared the efficacy and tolerability of 500 mg/day of calcium in the form of osseinhydroxyapatite (OHC) versus 500 mg/day of tricalcium phosphate (TCP) and placebo in the prevention of postmenopausal bone loss. OHC increased bone density by 0.8 percent at the spine at 12 months.

CONCLUSION: While both OHC and TCP were well tolerated and significantly reduced bone turnover markers, the effect of ossein hydroxyapatite seems slightly superior to that of tricalcium phosphate.

—19996—Preventing postmenopausal bone loss with ossein-hydroxyapatite compounds. Results of a two-year, prospective trial.

RESULTS: Sixty postmenopausal women were included in an open study and were allocated to three groups. The first group (n = 19) received treatment consisting in 3.32 g/d of OHC per day, the second group (n = 21) received 2.5 g of calcium carbonate per day, and the third group (n = 20) was a treatment-free control group. The control group exhibited significant loss of BMD in both the first and second years of treatment. The calcium carbonated group exhibited significant loss of BMD in the second year. The OHC group did not exhibit any significant change in BMD over the two years of the trial.

CONCLUSION: Continuous administration of OHC prevents bone loss in postmenopausal women.

Results similar to the above have been published with regard to trabecular bone loss in women with osteoporosis (Ruegsegger 1995)7, and so forth and so on dating back to the early 1980s—there have been at least 18 controlled studies. Results have consistently favored OHC for bone health and consistently favored OHC when compared with other forms of calcium supplementation.

BEYOND CALCIUM? As reported in the earlier article, the bioavailability of calcium seldom exceeds approximately 30 percent regardless of the source. If calcium by itself is not the sole source of benefits to bone health, then one implication is that a natural bone source of calcium may be superior to processed and purified sources.

Using the protein fraction of specific natural form of calcium supplement produced according to an exacting procedure (ossein hydroxyapatite complex or OHC from microcrystalline hydroxyapatite / MCHA), scientists at the University of Auckland have demonstrated this non-calcium component leads to:

stimulation of bone producing cells to increase bone formation (i.e., increase bone mineral density/BMD)

stimulation of the formation of other elements associated with bone health—these other markers are associated with bone quality as well as bone quantity (BMD)

This natural source of calcium, when formulated into a health product, is capable of retaining the same protein “fingerprint” found in the tested natural ingredient. The importance of mechanisms of action is that these help to explain clinical results in which on a gram-per-gram basis ossein hydroxyapatite complex (OHC) repeatedly has proved to be superior to other sources of calcium. Undenatured bone includes the combination of an inorganic calcium lattice of microcrystalline hydroxyapatite (MCHA) within an organic protein environment rich in naturally occurring growth factors. These growth factors help to explain the “bone quality” results found with MCHA/OHC.

MECHANISMS OF ACTION—REVEALING PRECLINICAL FINDINGS8

The University of Auckland studies on ossein hydroxyapatite complex (OHC) were based on the protein fractions and not the calcium found in bone. These protein fractions contain a variety of growth factors, including bone morphogenic proteins. After painstakingly separating the protein components from the calcium, several tests were performed. In one, it was observed that the protein digest dose-dependently increased the area of mineralized bone formed through stimulation of osteoblast differentiation. New bone matrix was laid down and mineralized.

A second experiment looked at the stimulation of gene expression for bone formation markers. This included in this model changes to Collagen Iα 1, OPG (osteoprotegrin), RunX2 and iBSP (bone sialoprotein) gene expression. Runx2 is a key transcription factor in the early stages of osteoblast differentiation. Also found to be increased was an inhibitor of osteoclasts, that is, an inhibitor of the cells that remodel (tear down) bone.

The conclusion of the researchers was that their studies suggest that the proteins present [independent of calcium per se] increased bone formation and osteoblastic cell function. There was a short-term decrease in osteoblast cell proliferation due to activation/differentiation while as new bone was being formed.

The results demonstrated “the potential to act as an anabolic factor of bone formation, in a similar manner to parathyroid hormone (PTH) which decreases osteoblast proliferation but significantly increases osteoblast mineralisation.” [sic]

FIVE KEY BENEFITS Individuals who are going to the trouble of supplementing their diets with nutrients for bone health usually are more interested in the “payoff” or benefits of their supplements than they are in mechanisms of action. Mechanisms can be complicated and unclear in their implications. Benefits are, well, benefits. Here are five worth considering:

1. Clinically demonstrated to deliver the same levels of efficacy as both calcium carbonate and calcium citrate as measured by the ability to suppress key markers of bone turnover (bone resorption).

After 90 days of continuous supplementation, the New Zealand bone-derived materials suppressed CTX and P1NP, two key makers of bone turnover, by an identical amount to calcium carbonate and calcium citrate.

2. Calcium not modified artificially, but presented in a natural food form.

The New Zealand-sourced bone-derived OHC/calcium source has been designed, developed and clinically proven to deliver calcium in a 100 percent natural protein complex which the body is able to digest, as it would a food, releasing the calcium slowly and steadily into the body.

3. Calcium is delivered to the bones without blood spikes.

Given recent concerns regarding serum calcium levels and cardiovascular health, this benefit, if nothing else, gives peace of mind. In a clinical trial in New Zealand, peak blood calcium levels after ingestion of a bone calcium preparation9 by study participants were 45 to 49 percent lower than peak blood calcium levels after ingestion of the same amount of calcium from either calcium carbonate or calcium citrate.

4. Demonstrated ability to promote bone matrix deposition and mineralization (bone formation).

As noted above, proteins extracted from the New Zealand-sourced bone-derived OHC/ calcium source in university trials demonstrated osteoinductivity, the ability to stimulate bone formation, as measured by osteoblast (bone cell) differentiation and mineralization in vitro.

5. Independent testing has verified the presence of critically important bone stimulating growth factors and bone matrix proteins

Unlike refined calcium supplements, such as calcium citrate and calcium carbonate, the New Zealand-sourced bone-derived OHC/calcium source contains protein (25 percent on average) rich in essential bone matrix components, including Type I collagen, osteocalcin and bone stimulating growth factors. Specifically, testing has verified the presence of the osteoinductive growth factors IGF I and 2, and TGFb 1 and 2. And, again, the collagen component should not be ignored. Type I collagen has been found to enhance osteoblast differentiation. Further, the combination of type I collagen and hydroxyapatite has been shown to accelerate osteogenesis.10

CONCLUSIONS The results to date in clinical and other work utilizing bone-derived OHC/ calcium have been impressive. There is no guesswork as to whether faster absorption or higher blood calcium levels should be considered markers for bone benefits inasmuch as bonederived OHC/calcium have been proved to deliver bone support. Moreover, that support extends beyond bone mineral density — bone quantity — to include support for the non-calcium elements of the structure of living bone —bone quality. For women worried about osteoporosis and bone fracture issues, this is not just bone support; it is support for peace of mind.

References:

1. (Am J Clin Nutr. 2011 Oct;94(4):1144–9)(BMJ. 2011 May 24;342:d1473.) (Am J Clin Nutr 2007;86:1780–90) (N Engl J Med. 2006 Feb 16;354(7):669–83)

2. Clin Drug Investig. 2011 Dec 1;31(12):817–24. 3. Menopause. 2009 Sept–Oct;16(5):984-91. 4. Clin Drug Investig. 2007;27(4):227–32. 5. Climacteric. 2004 Mar;7(1):33–40. 6. J Reprod Med. 1999 Jul;44(7):601–5. 7. Osteoporos Int. 1995 Jan;5(1):30–4. 8. 8 Musson, D.S., Watson, M., Callon, K. E. and Cornish, J. Preliminary study on

the role of MCH-Cal on osteoblast growth and differ entiation. Bone and Joint Group, University of Auckland.

9. Supplied by Waitaki Biosciences. 10. Wahl D.A., and Czernuszka J.T., Collagnehydroxyapa titew composites for hard

tissue repair. European Cells and Materials. 2006,11,43–56.

Comparison of the effects of ossein-hydroxyapatite complex and calcium carbonate on bone metabolism in women with senile osteoporosis: a randomized, open-label, parallel-group, controlled, prospective study.

Clin Drug Investig. 2011 Dec 1;31(12):817-24. Abstract BACKGROUND AND OBJECTIVE: Calcium and vitamin D supplementation is recommended in patients with osteopenia and osteoporosis. One group that could benefit from this treatment is women with senile osteoporosis. Two sources of supplementary calcium are ossein-hydroxyapatite complex (OHC) and calcium carbonate, but, to date, their comparative effects on bone metabolism have not been studied in women with senile osteoporosis. The objective of this study was to compare the effects of OHC and calcium carbonate on bone metabolism in women with senile osteoporosis.

METHODS: This was a randomized, open-label, parallel-group, controlled, prospective study to compare the effects of OHC (treatment group) and calcium carbonate (control group) on bone metabolism. Patients were included between 2000 and 2004 and followed up for a maximum of 3 years. The study was carried out at the bone metabolism unit of two university hospitals in Barcelona, Spain. Subjects were women aged >65 years with densitometric osteoporosis of the lumbar spine or femoral neck. The treatment group received open-label OHC (Osteopor®) at a dose of two 830 mg tablets every 12 hours (712 mg elemental calcium per day). The control group received open-label calcium carbonate at a dose of 500 mg of elemental calcium every 12 hours (1000 mg elemental calcium per day). Both groups also received a vitamin D supplement (calcifediol 266 μg) at a dose of one vial orally every 15 days. Biochemical markers of bone remodelling (osteocalcin by electrochemiluminescence, tartrate-resistant acid phosphatase using colorimetry) were measured at baseline and annually for 3 years. Bone mineral density (BMD) at the lumbar spine and femoral neck was also measured.

RESULTS: One hundred and twenty women were included (55 in the OHC group and 65 in the calcium carbonate group), of whom 54 completed 3 years of follow-up. Levels of serum osteocalcin increased to a greater extent in the OHC group compared with the calcium carbonate group (by a mean ± SD of 0.84 ± 3.13 ng/mL at year 2 and 1.86 ± 2.22 ng/mL at year 3 in the OHC group compared with a mean ± SD decrease of 0.39 ± 1.39 ng/mL at year 2 and an increase of 0.31 ± 2.51 ng/mL at year 3 in the calcium carbonate group); the differences between treatment groups were statistically significant (p < 0.05) at both years. Changes over time in serum osteocalcin level were also statistically significant (p < 0.05) in the OHC group, but not in the calcium carbonate group. Changes in mean

BMD at the lumbar spine and femoral neck between baseline and year 3 were -1.1% and 2.5% for OHC and -2.3% and 1.2% for calcium carbonate, respectively.

CONCLUSION: OHC had a greater anabolic effect on bone than calcium carbonate

Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis.

Menopause. 2009 Sep-Oct;16(5):984-91.

Abstract OBJECTIVE: There is increasing evidence to suggest that ossein-hydroxyapatite complex (OHC) is more effective than calcium supplements in maintaining bone mass. The aim of this meta-analysis was to determine whether OHC has a different clinical effect on bone mineral density (BMD) compared with calcium carbonate (CC).

METHODS: A meta-analysis of randomized controlled clinical trials was carried out to evaluate the efficacy of OHC versus CC on trabecular BMD. We identified publications on clinical trials by a search of electronic databases, including MEDLINE (1966-November 2008), EMBASE (1974-November 2008), and the Cochrane Controlled Clinical Trials Register.The primary endpoint was percent change in BMD from baseline. Data were pooled in a random-effects model, and the weighted mean difference was calculated. A sensitivity analysis that excluded trials without full data was performed.

RESULTS: Of the 18 controlled trials initially identified, 6 were included in the meta-analysis. There was no significant heterogeneity among the included trials. The percent change in BMD significantly favored the OHC group (1.02% [95% CI, 0.63-1.41], P < 0.00001). These results were confirmed in the sensitivity analysis.

CONCLUSIONS: OHC is significantly more effective in preventing bone loss than CC.

Preventing postmenopausal bone loss with ossein-hydroxyapatite compounds. Results of a two-year, prospective trial.

J Reprod Med. 1999 Jul;44(7):601-5. Abstract OBJECTIVE: To evaluate, in postmenopausal women who refuse hormone replacement therapy (HRT), whether continuous administration of an osseinhydroxyapatite compound (OHC) reduces bone loss and protects from osteoporosis.

STUDY DESIGN: Sixty postmenopausal women were included in an open study and were allocated to three groups. The first group (n = 19) received treatment consisting in 3.32 g/d of OHC per day, the second group (n = 21) received 2.5 g of calcium carbonate per day, and the third group (n = 20) was a treatment-free control group. Bone mineral density (BMD), assessed by dual x-ray absorptiometry, was measured prior to and at 12 and 24 months of treatment.

RESULTS: Subjects on OHC therapy did not show significant changes related to baseline on bone mass across the study, whereas a significant decrease was detected in the calcium carbonate group during the second year (-3.7%, P < .05) and in the control group at the first and second BMD measurement (-3.5%, P < .05; -5.6%, P < .01).

CONCLUSION: Continuous administration of OHC prevents bone loss in postmenopausal women, suggesting that this drug may be useful in the management of postmenopausal bone loss.

Prevention of osteoporosis: four-year follow-up of a cohort of postmenopausal women treated with an ossein-hydroxyapatite

compound. Clin Drug Investig. 2007;27(4):227-32.

Abstract BACKGROUND: The long-term effects of ossein-hydroxyapatite compound (OHC), a drug used for osteoporosis prevention, have not been previously reported. The aim of this study was to assess the long-term efficacy of OHC in postmenopausal women with bone mineral density (BMD) in the osteopenia range.

METHODS: We performed a retrospective 4-year follow-up study in a primary-care setting to assess changes in BMD in a cohort of 112 postmenopausal women included in an osteoporosis programme that included health and dietary advice and who were treated with OHC 1660mg every 12 hours. BMD was measured annually in the distal part of the forearm, with T- and Z-score values being calculated for trabecular and total bone.

RESULTS: A progressive and statistically significant increase in BMD was observed in trabecular and total T- and Z-score mean values. At baseline, mean +/- SD trabecular T- and Z-scores were -1.27 +/- 0.7 and -1.03 +/- 0.7, respectively, and -0.86 +/- 0.7 and -0.62 +/- 0.7, respectively, at the end of the 4-year follow-up period (both p < 0.0001). Mild constipation was observed in 3.2% of patients during the follow-up period.

CONCLUSION: Ossein-hydroxyapatite compound could be an effective and safe agent for the prevention of bone loss in postmenopausal osteopenic women, with significant increases in BMD being observed in this group of patients.

Effects of ossein-hydroxyapatite compound on ewe bone remodeling: Biochemical and histomorphometric study

Clinical Rheumatology September 1991, Volume 10, Issue 3, pp 269-273

Summary Ossein-hydroxyapatite compound (OHC) is a protein-mineral complex derived from bovine bone. Its effects on bone remodeling were studied in old ewes which have seasonal variations in bone remodeling. Seven animals received 200 mg OHC/kg b.w./day for 90 days from July to September. The control group consisted of 7 untreated animals followed for the same period of time. OHC was administered through a fistula into the fourth stomach. A significant decrease of bone histomorphometric parameter values was noted in controls at the end of the experiment, due to seasonal variations: the cancellous eroded perimeter decreased by 45%, the osteoblastic perimeter by 60% and the bone formation rate at the cell level by 20%. In contrast, in the treated-group, these parameters tended to increase or did not change. In conclusion, counteracting the significant seasonal reduction of bone remodeling in ewes, OHC seems able to stimulate directly or indirectly bone metabolism, especially when osteoblast activity is reduced and may partly prevent the seasonal reduction of bone turnover.

Effect of the ossein-hydroxyapatite complex on fracture consolidation under protein malnutrition: experimental study using rats

Acta ortop. bras. vol.9 no.2 São Paulo Apr./June 2001

SUMMARY

Assessment of the effect of ossein-hidroxiapatite compound in the fracture healing under protein malnutrition: experimental essay in rats.

An experimental essay was carried out with 40 Wistar male rats to assess the effect of the ossein-hidroxiapatite compound (OHC) in the fracture healing in animal under protein diet and no protein diet, which were divided into four groups, at random, which received or did not receive the compound. Each group with 10 animals, was divided into: group I, protein diet, without OHC; group II, protein diet, with OHC; group III, no protein diet, without OHC; group IV, no protein diet, with OHC. The fractures were made similarly as to the trace and site in all groups in the 15th day, when groups II and IV started receiving a daily dose of 20mg of the OHC, orally. Blood samples were drawn from all groups on the 1st , 15th and 43rd days. The animals underwent euthanasia on the 43rd day. Weight control as well as calcium, phosphorus, alkaline phosphatase total proteins, albumin, and osteocalcine were determined. The fractured limb was desarticulated in the hip joint on the 43rd day, and the bone callus was submitted to histological, histomorphometric, radiographic, planimetric and densitometric examination. It was concluded, after statistical analysis, that the OHC did not interfere significantly, in general assessment in bone callus formation in malnutrition and nourished animals. However it showed significant interference in some results such as albumin and alkaline phosphatase blood samples, in the planimetry and weight of the animals.

Comparison of the Treatment Effects of Ossein Hydroxyapatite Compound and Calcium Carbonate in Osteoporotic Females.

Osteoporosis International 5: 30-34. This study demonstrated that microcrystalline (ossein) hydroxyapatite was more effective in preventing further bone loss in osteoporosis patients than calcium carbonate. It is suggested that these effects are attributed to osteogenic effects of the organic component found in natural calcium hydroxyapatites. Another reason may also be the excellent bioavailability as has been demonstrated in other studies. The absence of side effects is also desirable, which would enable long-term treatments (Refer page 33 of discussion).

Comparison of the effects of two different types of calcium supplementation on markers of bone metabolism in a post-menopausal

osteopenic population with a low calcium intake:a double blind placebo-controlled trial.

Climacteric: 7 (1):33-40

This study compared the efficacy and tolerability of 500mg/day of calcium in the form of ossein hydroxyapatite (OHC) versus 500mg/day of tricalcium phopspate (TCP) and placebo in the prevention of post menopausal bone loss. This was a prospective randomized study enrolling 153 post menopausal osteopenic women. Serum and urine markers of bone turnover were collected at 3 and 6 months. Bone density was measured at baseline and 6 months in all participants, and at 12 months in women taking OHC. At 3 and 6 months, both TCP and OHC decreased serum markers of bone formation significantly, compared with placebo. At 6 months TCP and OHC decreased osteocalcin by 9.9% and 12.3% respectively; the aminoterminal propeptide of type 1 collagen (PINP) was decreased by 5.3% and 6.3%, respectively: bone specific alkaline phosphotase was decreased by 4.3% and 6.7%, respectively, compared with baseline. The effects on bone resorbtion markers or on bone mineral density did not reach statistical significance , however OCH increased bone density by 0.8% at the spine at 12 months. Both forms of calcium were well tolerated and did not differ from placebo in terms of side effects. It was concluded whilst OHC and TCP were well tolerated and significantly reduced bone turnover markers the effect of ossein hydroxyapatite seems slightly superior to that of tri calcium phosphate

Annefeld M, Caviezel R, Schacht E, Schicketanz KH 1986 The Influence of Ossein Hydroxyapatite compound on the Healing of a Bone Defect

Current Medical Research and Opinion Vol 10, No4. This animal study was undertaken to determine the effects of ossein hydroxyapatite compound (OHC) in bone healing. Standardized bony defects were produced and the animals were randomized into 4 groups. Group one was administered 830mg/day OMC, a second group received an ashed OMC (organic fraction destroyed) 510mg/day, the third group received 650mg/day calcium carbonate. The final group was the control. A series of fluorescent markers was administered to the animals in each group from the 7th to the 32nd day after production of the defect. A third of the animals in each group were sacrificed at 35,56 and 84 days respectively after the induction of the defect. Histological sections of the bone defect area were examined with a fluorescence microscope and resulting photomicrographs were scored with respect to degree of fluorescence, nature and degree of defect filling and structure of the newly formed bone. Treatment with OHC, but not the other 2 active treatments, resulted in significant improvements in the pattern and quality of the bone healing, particularly when assessed at 56 and 84 days after the induction of the defect. These results suggest that intact OMC has a beneficial effect on the process of bone healing but this effect is lost if the organic components are removed or if pure calcium carbonate treatment is substituted. It also suggests that components of intact OMC have osteogenic effects that enhance the uptake of the mineral component.

Castelo-Branco C, Pons F, Vicente JJ, Sanjuan A, Vanrell JA 1999 Preventing Postmenopausal Bone Loss with Ossein Hydroxyapatite

CompoundsResults of a Two-Year, Prospective Trial. Journal of Reproductive Medicine.

This study set out to evaluate in postmenopausal women who refuse HRT wether continuous administration of OHC reduces bone loss and protects from osteoporosis. Sixty postmenopausal were included in the open study and allocated to 3 groups. The first group received 3.32g/day OHC, the second group received 2.5g/day of calcium carbonate and the third group was a treatment free control. Bone Mineral Density (BMD) was accessed by dual x-ray absorptiometry and was measured prior

to and at 12 and 24 months of treatment. Subjects on the OHC did not show significant changes related to baseline on bone mass across the study however a significant decrease was detected in the calcium carbonate group in the second year and in the control group at the first and second BMD measurement. Although the results were not significant for OHC in this particular study the authors still concluded that the continuous administration of OHC is effective in the prevention of bone loss in a portion of postmenopausal women and may be superior to conventional calcium supplementation. Castelo- Branco C, Martinez de Osaba MJ, Pons F, Casals E, Sanjuan A, Vicente JJ,

Vanrell JA. 1999. Ossein-Hydroxyapatite Compounds for Preventing Postmenopausal Bone Loss.

Co adjuvant Use with Hormone Replacement Therapy The Journal of Reproductive Medicine Vol 44, No3.

The objective of this study was to evaluate whether the addition of an ossein-hydroxyapatite compound (OHC) might improve the effect of hormone replacement therapy (HRT) on postmenopausal bone loss. Of the 118 recent surgically post-menopausal women initially selected for this open study, 96 completed 1 year follow up. Patients were allocated into four groups. The first group received 50mcg/d of transdermal 17-beta estradiol continuously (group E), the second received 3.32g/day of OHC every day (group OHC), the third received 50mcg/day of transdermal 17-beta estradiol continuously plus 3.32g/day of OHC every day (group E-OHC). An additional 24 women were used as untreated controls. Bone mass was accessed by dual x-ray absorptiometry, was measured prior to and at the end of treatment. Samples including serum calcium, phosphate and osteocalcin level were collected before therapy and during the 6th and 12th treatment months. Results from this study showed an increase in bone mineral content in all treatment groups however the increase was highest in the E-OHC group. The authors concluded that the combined regime of OHC and HRT increased vertebral bone mass in postmenopausal women to a greater extent than did OHC or HRT alone. Whilst this study might not hold either OMC or HRT in good light as stand alone treatments the author does comment on the historical pharmacologic treatment options (HRT, calcitonin, vitamins and mineral supplements). HRT has been the logical choice since the high turnover of trabecular bone that follows menopause is related to the decline in estradiol levels. HRT however is not a panacea for bone loss related to menopause and to be completely effective needs to be accompanied by a wide range of other considerations (lifestyle, diet, exercise). Despite some success with HRT to date the best overall scheme for treatment is still under discussion. Calcium alone is not enough for bone resorption so adding just calcium to HRT will

not significantly improve results. OHCs are a protein –mineral complexes and have been shown in animal and human studies to have positive effects on bone remodelling and have been also been shown to be more effective that calcium in slowing peripheral trabecular bone loss.

Pines A, Raafat H, Lynn AH, Whittington J 1984. Clinical Trial of Microcrystalline Hydroxyapatite compound (MCHC) in the

Prevention of Osteoporosis due to Corticosteroid Therapy. Current Medical Research and Opinion Vol 8 No10.

A clinical trial that was carried out on 40 patients at risk of osteoporosis due to long term treatment with prednisolone to determine the efficacy and tolerance of MCHC when used to prevent the appearance or progression of osteoporosis. 32 patients were treated with 6-8g MCHC for 12months and 8 served as an untreated control group. 37 patients successfully completed the trial. 68% of the patients had back pain prior to trial, the severity of which was graded at 3 month intervals. In the MCHC group thaere was a significant reduction in pain during the trial, almost to the point of disappearance. Of 19 patients with initial back pain only 2 still reported any pain after 12 months of MCHC treatment. In the control group back pain severity increased during the trial in 3 patients and was unchanged in the fourth. Neither group showed any significant change in standing height during the 12-month trial. Both mean cortical thickness and metacarpal index figures showed small insignificant decreases in the MCHC group but much more marked decreases in the control group. There were no reports of drug related side effects in the MCHC group and renal and hepatic function revealed no signs of toxicity during MCHC therapy. Significant increases in serum calcium and phosphate levels were detected in the MCHC group thus providing the necessary biochemical environment for bone remineralization. The author comments in the discussion that the ultimate result would be effective treatment and prevention of osteoporosis, the reduction of complications, particularly fractures of the vertebral column, wrist and hip. However a study to examine these ultimate effects would require a very large number of at risk patient's studies over a number of years. No patients in the study developed a clinical fracture. To obtain the information on efficacy of MCHC on the indices of osteoporosis, which can be, expected to change of a shorter time course (skeletal pain, height and direct measurements by radiographic methods). Clearly the MCHC group experienced a progressive reduction in back pain that the author described as dramatic in contrast to the control group that showed a small increase in pain. The bone indices from the radiographs gave indications that the MCHC treatment was stopping or slowing the progression of osteoporosis. The small and insignificant deteriorations during MCHC

treatment contrasted with the greater deteriorations in the control group. Standing and stem height measurements did not show appreciable gains however this was expected given the short duration and the fact patients were not in an accelerated phase of osteoporosis progression. The study concluded that there was a tolerance to the MCHC by patients, that MCHC dramatically reduced skeletal pain in patients developing osteoporosis and presented strong evidence that the symptomatic improvements were associated with both favourable biochemical and radiological bone changes.

Stepan JJ, Poshichal J, Presl and Pacovsky V. 1989 Department of Internal Medicine 3, Charles University of Medicine and Institute

for Care of Mother and Child. Prague, Czechoslovakia. Prospective Trial of Ossein Hydroxyapatite Compound (OHC) in Surgically

Induced Postmenopausal Women. Bone, 10, 179-185.

48 Caucasian women who had undergone surgically induced increase in bone resorption 1-5 years previously (hysterectomy with bilateral oophorectomy because of benign uterine disease) were divided into a control group (20) and treatment group (28) were studied during a 3-year follow up. The OHC treatment provided 1.6g calcium, 0.74g phosphorus and 1.94g non-collagen peptides per day. All subjects had regular menstrual patterns prior to oophorectomy, none had past or present history of any disease that alters the skeleton or had been treated with sex hormones or other drugs known to influence calcium metabolism. The patients were 2.6years post menopausal and status was confirmed by testing for elevated levels of follicle–stimulating hormone. The objective was to secure a population with increased bone resorption. In such a population bone loss (resorption) was more likely to be prevented and the effects of the OHC more likely to be statistically demonstrable. Biochemical indices of bone remodelling (urinary hydroxyproline/creatine and calcium/creatine ratios, bone alkaline phosphatase isoenzyme in serum and plasma tartrate resistant phosphatase) decreased significantly in both treatments and control groups compared to base line values. Biochemical indices were significantly lower in the treatment group compared to the controls after the first year, but in only half the patients after 3 years. By the third year these responders had significantly higher cortical area than controls. The results supported the conclusion that OHC was effective in decreasing bone loss in the patients. The conclusion being based on a decrease is bone resorption and is determined by biochemical markers and a decrease in bone loss as determined by radiogrammetric studies. There were however a sub group of patients who only

showed a temporary decrease in biochemical indices of bone resorption and in bone loss rate. This could not be conclusively attributed to treatment non-compliance nor was it believed to be poor absorption because of the subsets early response to OHC. It was possible that the calcium supplements corrected a pre-existing condition of calcium deficiency of the mineral bone phase however this was discounted, as it would not account for the early decrease in bone resorption indices. Regardless OHC treatment in the responders favourably alters the abnormal pattern of cortical bone remodelling yet long-term studies are required to determine wether it reduces morbidity associated with osteopenia.

Percival M 1999 Bone Health & Osteoporosis

Applied Nutritional Science Reports Vol 5, No4

An interesting discussion paper that outlines the risk factors for osteoporosis, the studies to date concerning maximizing peak bone mass, the reduction of bone loss is post menopausal women, recommended daily allowances, calcium absorption and

the role of Vitamin D, magnesium and other trace minerals.

The author provides an overview of the research to date on MCHC, the beneficial features and comprehensive guidelines for accessing the purity of MCHC.

Chavassieux P, Pastoureau, Boivin G, Delams PD, Chapuy MC, Meunier PJ 1991 Effects of Ossein-hydroxyapatite compound on ewe bone remodelling: biochemical

and histomorphometric study Clin Rheumatology 10(3):269-73

The effects of ossein hydroxyapatite compound (OHC) on bone remodelling were studied in old ewes which have seasonal variations in bone remodelling. Seven animals received 200mg OHC/kg b.w/day for 90 days from July to September. The control group consisted of 7 untreated animals followed for the same period of time. OHC was administered via a fistula inot the fourth stomach. A significant decrease of bone histomorphometric parameter values was noted in controls ant the end of the experiement , due to seasonal variations: the cancellous eroded perimeter decreased by 45%, the osteoblastic perimeter by 60% and the bone formation rate at the cell level by 20%. In contrast, the treated group, these parameters tended to increase or did not change. It was concluded, counteracting the significant seasonal reduction of bone remodelling in ewes, OHC seems able to stimulate directly or indirectly bone metabolism, especially when osteoblast activity is reduced and may partly prevent

the seasonal reduction of bone turnover.

Schmidt KH,Worner UM, Buck HJ 1988 Chirurgische Universitatsklinik, Tubingen, Federal Republic of Germany

Examination of new bone growth on aluminium oxide implant contact surfaces after oral administration of ossein-hydroxyapatite compound to rats.

Current Medical Research Opinion 11(2):107-15 This study was under taken to examine whether the oral administration of osseinhydroxyapatite compound (OHC) could stimulate new bone growth on aluminium oxide implant surfaces and if so, whether it was the mineral or organic part of the compound that was responsible. Adult white male Wistar rats had 2 implants fitted whilst under anaesthesia. The animals wee divided into 5 groups each of 5 rats and the groups received oral daily doses of 20mg OHC, 100mg OCH, 10mg hydroxyapatite, 50mg hydroxyapatite or no supplement (control), respectively. After 20 days, each implant was evaluated by 5 cuts through the marrow area and the thickness of the newly grown layer of bone measured by a morphometric procedure. The results showed a significant increase in new bone growth for the 100mg OHC group in comparison to the control group and in comparison to the hydroxyapatite. Because both supplement groups received equivalent dosages of calcium and phosphorus (present in OCH and hydroxyapatite), the additional stimulation of new bone growth must have been due to the organic part of OHC (ossein). It is suggested by the authors that these results should stimulate the clinical use of OHC in the critical intial phase of implant healing and delayed fracture healing. Other Related Research Stellon A, Davies A, Webb A, Williams R 1985 Microcrystalline Hydroxyapatite compound in prevention of bone loss in corticosteroid treated patients with chronic active hepatitis Postgrad Med J 61 (719a:791-6 Hill PA, Reynolds JJ, Meikle MC 1995 Osteoblasts mediate insulin like growth factor I and II stimulation of osteoclast formation and function Endocrinology: 136(1):124-31 Baylink DJ, Finkelman RD, Mohan S 1993 Growth Factors to Stimulate Bone Formation J Bone Miner Res Suppl 2: S565-72 Mohan S, Baylink DJ 1991

Bone Growth Factors Clin Orthop 263: 30-48 Millis DL 1999 Bone and non-bone derived growth factors and effects on bone healing Vet Clin North Am Samll Anim Pract 29 (5);1221-46 Canalis E, Mc CarthY T, Centrella M 1988 Isolation of growth factors from adult bovine bone Calcif Tissue Int 43 (6):346-51 Linkhart TA, Jennings JC, Mohan S, Wakley GK, Baylink DJ 1986 Characterization of the mitogenic activities extracted from bovine bone matrix Bone: 7 (6): 479-87 Hauschaka PV, Chen TL, Mavrakos AE 1988 Polypeptide growth factors in bone matrix Ciba Fond Symp 136:207-25 Termine JD 1988 Non Collagen proteins in bone Ciba Fond Symp 136: 178-202 Takeuchi Y, Kodama Y, Matsumoto T 1994 Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity J Biol Chem ; 269 A(51):32634-8

Prepared by :Asma Saleem