Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.
Climacteric. 2015 Feb;18(1):29-37.
Castelo-Branco C, Dávila Guardia J.
Background and objective The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions.
Material and methods A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists.
Results Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis.
Conclusion The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.
Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.
Br J Nutr. 2014 Nov 28;112(10):1611-20.
Bristow SM, Gamble GD, Stewart A, Horne L, House ME, Aati O, Mihov B, Horne AM, Reid IR.
Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.
Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women.
Nutr J. 2012 Nov 12;11:93.
Sato T, Schurgers LJ, Uenishi K.
BACKGROUND: Vitamin K? contributes to bone and cardiovascular health. Therefore, two vitamin K? homologues, menaquinone-4 (MK-4) and menaquinone-7 (MK-7), have been used as nutrients by the food industry and as nutritional supplements to support bone and cardiovascular health. However, little is known about the bioavailability of nutritional MK-4. To investigate MK-4 and MK-7 bioavailability, nutritional doses were administered to healthy Japanese women.
FINDINGS: Single dose administration of MK-4 (420 μg; 945 nmol) or MK-7 (420 μg; 647 nmol) was given in the morning together with standardized breakfast. MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point. Consecutive administration of MK-4 (60 μg; 135 nmol) or MK-7 (60 μg; 92 nmol) for 7 days demonstrated that MK-4 supplementation did not increase serum MK-4 levels. However, consecutive administration of MK-7 increased serum MK-7 levels significantly in all subjects.
CONCLUSIONS: We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues.
Essential Nutrients for Bone Health and a Review of their Availability in the Average North American Diet.
Open Orthop J. 2012;6:143-9.
Price CT, Langford JR, Liporace FA.
Osteoporosis and low bone mineral density affect millions of Americans. The majority of adults in North America have insufficient intake of vitamin D and calcium along with inadequate exercise. Physicians are aware that vitamin D, calcium and exercise are essential for maintenance of bone health. Physicians are less likely to be aware that dietary insufficiencies of magnesium, silicon, Vitamin K, and boron are also widely prevalent, and each of these essential nutrients is an important contributor to bone health. In addition, specific nutritional factors may improve calcium metabolism and bone formation. It is the authors’ opinion that nutritional supplements should attempt to provide ample, but not excessive, amounts of factors that are frequently insufficient in the typical American diet. In contrast to dietary insufficiencies, several nutrients that support bone health are readily available in the average American diet. These include zinc, manganese, and copper which may have adverse effects at higher levels of intake. Some multivitamins and bone support products provide additional quantities of nutrients that may be unnecessary or potentially harmful. The purpose of this paper is to identify specific nutritional components of bone health, the effects on bone, the level of availability in the average American diet, and the implications of supplementation for each nutritional component. A summary of recommended dietary supplementation is included.
Changes in parameters of bone metabolism in postmenopausal women following a 12-month intervention period using dairy products enriched with calcium, vitamin D, and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): the Postmenopausal Health Study II.
Calcif Tissue Int. 2012 Apr;90(4):251-62.
Kanellakis S, Moschonis G, Tenta R, Schaafsma A, van den Heuvel EG, Papaioannou N, Lyritis G, Manios Y.
The objective of the present study was to examine the effect of dairy products enriched with calcium, vitamin D(3), and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K(2)) on parameters of bone metabolism in postmenopausal women following a 12-month intervention. Postmenopausal women were divided into three intervention groups and a control group (CG). All three intervention groups attended biweekly sessions and received fortified dairy products providing daily 800 mg of calcium and 10 μg of vitamin D(3) (CaD). Furthermore, in two of the three intervention groups the dairy products were also enriched with vitamin K, providing daily 100 μg of either phylloquinone (CaDK1) or menaquinone-7 (CaDK2). The increase observed for serum 25(OH)D levels in all intervention groups and the increase observed for serum IGF-I levels in the CaDK2 group differed significantly compared to the changes observed in CG (P = 0.010 and P = 0.028, respectively). Furthermore, both the CaDK1 and CaDK2 groups had a significantly lower mean serum undercarboxylated osteocalcin to osteocalcin ratio and urine deoxypyridinoline levels at follow-up compared to the CaD and CG groups (P = 0.001 and P = 0.047, respectively). Significant increases in total-body BMD were observed in all intervention groups compared to CG (P < 0.05), while significant increases in lumbar spine BMD were observed only for CaDK1 and CaDK2 compared to CG (P < 0.05) after controlling for changes in serum 25(OH)D levels and dietary calcium intake. In conclusion, the present study revealed more favorable changes in bone metabolism and bone mass indices for the two vitamin K-supplemented groups, mainly reflected in the suppression of serum levels of bone remodeling indices and in the more positive changes in lumbar spine BMD for these two study groups.
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.
Ciria-Recasens M, Blanch-Rubió J, Coll-Batet M, Del Pilar Lisbona-Pérez M, Díez-Perez A, Carbonell-Abelló J, Manasanch J, Pérez-Edo L.
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.
Castelo-Branco C, Ciria-Recasens M, Cancelo-Hidalgo MJ, Palacios S, Haya-Palazuelos J, Carbonell-Abelló J, Blanch-Rubió J, Martínez-Zapata MJ, Manasanch J, Pérez-Edo L.
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.
Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells.
J Mol Endocrinol. 2007 Oct;39(4):239-47.
Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S.
Vitamin K is known as a critical nutrient required for bone homeostasis and blood coagulation, and it is clinically used as a therapeutic agent for osteoporosis in Japan. Besides its enzymatic action as a cofactor of vitamin K-dependent gamma-glutamyl carboxylase (GGCX), we have previously shown that vitamin K(2) is a transcriptional regulator of bone marker genes and extracellular matrix-related genes, by activating the steroid and xenobiotic receptor (SXR). To explore a novel action of vitamin K in osteoblastic cells, we identified genes up-regulated by a vitamin K(2) isoform menaquinone-4 (MK-4) using oligonucleotide microarray analysis. Among these up-regulated genes by MK-4, growth differentiation factor 15 (GDF15) and stanniocalcin 2 (STC2) were identified as novel MK-4 target genes independent of GGCX and SXR pathways in human and mouse osteoblastic cells. The induction of GDF15 and STC2 is likely specific to MK-4, as it was not exerted by another vitamin K(2) isoform MK-7, vitamin K(1), or the MK-4 side chain structure geranylgeraniol. Investigation of the involved signaling pathways revealed that MK-4 enhanced the phosphorylation of protein kinase A (PKA), and the MK-4-dependent induction of both GDF15 and STC2 genes was reduced by the treatment with a PKA inhibitor H89 or siRNA against PKA. These results suggest that vitamin K(2) modulates its target gene expression in osteoblastic cells through the PKA-dependent mechanism, which may be distinct from the previously known vitamin K signaling pathways.
Vitamin D and Calcium Supplementation among Aged Residents in Nursing Homes.
J Nutr Health Aging. 2007 Sep-Oct;11(5):433-7.
Suominen MH, Hosia Randell HM, Muurinen S, Peiponen A, Routasalo P, Soini H, Suur Uski I, Pitkala KH.
Background: Aged residents in nursing homes are at particularly high risk of fractures. Vitamin D and calcium have a preventative role. Objective: To describe the use of vitamin D and calcium supplementations, and their association with nutritional factors among nursing home residents.
Methods: Our study is a cross-sectional assessment of long-term residents in all nursing homes in Helsinki during February 2003. We collected residents’ background information, nutritional status (Mini Nutritional Assessment, MNA), and data on daily nursing routines in institutions, including nutritional care. Vitamin D and calcium supplementations were inquired after in the questionnaire and retrieved from residents’ medication lists.
Results: 2 114 (87%) of all 2424 eligible residents had available data on the use of vitamin D and calcium supplementation. Their mean age was 83 years, and 80.7% were female. Of all participants, 32.9% received vitamin D supplementation and 27.7% calcium supplementation. Altogether 20.0% received both. However, only 21.3% received vitamin D in the therapeutic dose of 10mg (400 IU) or more, and 3.6% in the recommended dose of 20microg (800 IU) or more. In logistic regression analysis, residents who received vitamin D supplementation also had better nutritional status (MNA), ate snacks between meals, did not have constipation and their weight was checked more frequently.
Conclusions: Regardless of the known benefit and recommendation of vitamin D supplementation for the elderly residing mostly indoors, the proportion of nursing home residents receiving vitamin D and calcium was surprisingly low.
Potential benefit of oral calcium/vitamin d administration for prevention of symptomatic hypocalcemia after total thyroidectomy.
Endocr Regul. 2007 Mar;41(1):35.
Kurukahvecioglu O, Karamercan A, Akin M, Tezel E, Ege B, Taneri F, Onuk E.
Objective. To evaluate routine oral calcium and vitamin D administration for preventing symptoms of hypocalcemia after total thyroidectomy.
Subjects and methods. A total of 487 consecutive patients were prospectively randomized into two groups in terms of routine oral calcium and vitamin D supplementation: In the control group (244 patients) the treatment was not routinely started after surgery, whereas the treated group (243 patients) received routine supplementation that started on postoperative day 1.
Results. Patients of treated group had only minor hypocalcemia symptoms, whereas 7 patients of control group experienced carpopedal spasm as a major symptom (p Conclusions. Routine postoperative calcium and vitamin D supplementation therapy may be useful for the prevention of symptomatic hypocalcemia after total thyroidectomy and may allow for a safe and early discharge from the hospital. Keywords: Thyroidectomy Hypocalcemia Calcium – Vitamin D – Dietary supplementation.
Prevention of Osteoporosis: Four-Year Follow-Up of a Cohort of Postmenopausal Women Treated with an Ossein-Hydroxyapatite Compound.
Clinical Drug Investigation. 27(4):227-232, 2007.
Fernandez-Pareja A, Hernandez-Blanco E, Perez-Maceda JM, Riera Rubio VJ, Palazuelos JH, Dalmau JM.
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.