Ossein Mineral complex+vitamin D

2. 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.

3. 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.

4. 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.

5. 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:

6. 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

7. 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.

8. 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

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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 ossein
hydroxyapatite 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

21. 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