Effect of calcium phosphate compound (MZF-CaP) with and without fluoride in preventing bone loss in ovariectomized rats
Keywords:
Calcium phosphate, crystallinity, Osteoporosis, Zinc, FluorineAbstract
Zinc (Zn) has been shown to inhibit osteoclast differentiation, promote osteoblast activity, and enhance the bone formation. Zinc-containing calcium phosphate (Zn-TCP) implanted in rabbit femoral defect was demonstrated to stimulate bone formation. Other studies demonstrated that calcium phosphate compounds (MZF-CaP) incorporating magnesium (Mg2+), zinc and fluoride (F-) when administered either by injection or orally were effective in preventing bone loss (osteoporosis) induced by estrogen deficiency (ovariectomy) in a rat model. The objective of the present study was to investigate the preventive effect of similar compound, with F (MZF-CaP-L, MZF-CaP-H) and without F (MZ-CaP-L), when injected in ovariectomized (OVX) rats. MZF-CaP-L and MZ-CaP-L were prepared by precipitation at 90oC and MZF-CaP-H was prepared by sintering MZF-CaP-L at 900oC. The release of the ions from acidic buffer was determined. Suspensions of Zn-TCP, MZF-CaP-H, MZF-CaP-L and MZ-CaP-L (617 μg in 0.2 ml of 1% sodium alginate saline solution) were injected intramuscularly under anesthesia into 5-week-old OVX rats on Zn-deficient diet. One week after surgery, bone mineral density (BMD) and bone mineral content (BMC) of the rat femurs were measured using X-ray CT. The injections and X-ray CT and Zn ion plasma measurements were repeated every week for 12 weeks. The rats were sacrificed and the femurs removed after 12 weeks. Bone mechanical strength was evaluated using the three-point bending test. MZ-CaP-L (without F), compared to the other compounds, showed the highest increase in the Zn2+ ion plasma concentration, and the highest BMD, BMC and mechanical strength.
References
. Melton LJ III. Adverse outcomes of
osteoporotic fractures in the general
population. J bone Miner Res 2003; 18:
ă1141.
. Rodan Ga, Raisz LG, Milezikian JP.
Pathophysiology of Osteoporosis. In:
Bilexikian JP, Raisz LG, Rodan GA
(eds). Principles of Bone Biology. Acad
Press, New York. 1996; 979ă992.
. Fleisch H, Reszka A, Rodan GA ,
Rogers M. Bisphosphonates:
Mechanisms of Action. In: Bilezikian JP,
Raisz LG, Rodan GA (eds). Principles of
Bone Biology (2nd ed). Academic
Press;New York. 2002; 1361ă1386.
. Mauck KF, Clarke BL Diagnosis
screening, prevention and treatment of
osteoporosis. Mayo Clin Proc. 2005; 81:
-672.
. Kishi S, Yamaguchi M. Inhibitory effect
of zinc compounds on osteoblast-like
cell formation in mouse marrow cultures.
Biochem Pharmacol. 1994; 48: 1225ă
. Yamaguchi M, Inamoto K, Suketa Y.
Effect of essential trace metals on bone
metabolism in weanling rats:
Comparison with zinc and other metals'
actions. Res Exp Med. 1986; 186: 337ă
. Szathmari M, Steczek K, Szucs J, Hollo
I. Zinc excretion in osteoporotic women.
Orv Hetil. 1993; 134: 911ă914.
. Relea P, Revilla M, Pipoll E, Arribas I,
Villa LF, Rico H. Zinc, biochemical
markers of nutrition, and type I
osteoporosis. Age Aging. 1995; 24: 303ă
. Williams RJ. Zinc: What is its role in
biology? Endeavour. 1984; 8: 65ă70.
. Oner G, Bhaumick B, Bala RM. Effect of
Zinc Deficiency on Serum Somatomedin
Levels and Skeletal Growth in Young
Rats, Endocrinology. 1984; 114: 1860ă
. Shankar AH, Prasad AS. Zinc and
immune function: the biological basis of
altered resistance to infection. AM J Clin
Nutr. 1998; 68: 447Să463S.
. Ito A, Naito H, Ichinose N, Tateish T.
Preparation, solubility, and
cytocompatibility of zinc-releasing
calcium phosphate ceramics. J Biomed
Mater Res. 2000; 50: 178ă183.
. Kawamura H, Ito A, Miyakawa S,
Layrolle P, Ojima K, Naito H, et al.
Stimulatory effect of zinc on bone
formation around zinc-releasing calcium
phosphate ceramics implanted rabbits
femora. J Biomed Mater Res. 2000; 50:
ă190.
. LeGeros RZ. NIBIB/NIH grant number
EB 003070. 2007.
. LeGeros RZ. Apatites in Biological
Systems. Prog. Crystal Growth Charact.
; 4: 1ă45.
. LeGeros RZ. Calcium phosphates in oral
biology and medicine. In: Myers HM,
editor: Monogr Oral Sci. Basel: Karger.
; 82ă107.
. Wallach S. Effect of magnesium in
skeletal metabolism. Trace Elem. 1990;
: 1ă14.
. Kleerelopper M. Fluoride and the
skeleton. In: Bilezikian JP, Raisz LG,
Rodan GA, editors. Principles of bone
biology. Chapter 75. San Diego:
Academic Press. 1996; 1053ă1062.
. Otsuka M, Oshinbe A, LeGeros RZ,
Tokudome Y, Ito A, Otsuka K, Higuchi
WI . Efficacy of a new injectable calcium
phosphate ceramic suspension on
improving bone properties of
ovariectomized rats. J Pharm Sci. 2008;
: 421ă432.
. Tokudome Y, Otsuka M, Ito A, LeGeros
RZ. Long-term therapeutic effect of
novel calcium phosphate based
compounds injected in ovariectomized
rats. J Biomed Mater Res. 2009; 90B:
ă237.
. LeGeros RZ, Mijares D, Yao F, Tannous
S, Catig G, Xi Q, Dias R, LeGeros JP.
Synthetic bone mineral (SBM) for
osteoporosis therapy: Part I. Prevention
of bone loss from mineral deficiency.
Key Engineer Mater. 2008; 361-363: 43ă
Trans Tech Pub, Switzerland.
. Mijares D. Prevention of bone loss in
ovariectomized rat model: Effect of
synthetic bone mineral (SBM). MS
Thesis. New York University. 2010.
. Mijares D, Kulkarni A, Lewis K, Yao F, Xi
Q, Tannous S, Dias R, LeGeros RZ.
Oral bone loss induced by mineral
deficiency in a rat model: Effect of a
synthetic bone mineral (SBM)
preparation. Arch Oral Biol. 2012; 57:
ă1273.
. LeGeros RZ LeGeros JP, Trautz OR,
Shirra WP. Conversion of monetite,
CaHPO4, to apatites: effect of carbonate
on the crystallinity and the morphology
of the apatite crystallites. Adv X-ray Anal
; 14: 57ă66.
. LeGeros RZ, Bleiwas CB, Retino M,
Rohanizadeh R, LeGeros JP. Zinc effect
on the in vitro formation of calcium
phosphates: relevance to clinical
inhibition of calculus formation. Am J
Dent. 1999; 12: 65ă70.
. LeGeros RZ, Sakae T, Bautista C,
Retino M, LeGeros JP. Magnesium and
carbonate in enamel and synthetic
apatites. Adv Dent Res. 1996; 10: 225ă
. LeGeros RZ, Singer L, Ophaug RH,
Quirolgico G, Thein A, LeGeros JP. The
effect of fluoride on the stability of
synthetic and biological (bone mineral)
apatites. In Menzcel J, Robin GC, Makin
M, Steinberg R (eds.), Osteoporosis, J.
Wiley & Sons, New York: 1982; 327ă
. LeGeros RZ, Tung MS. Chemical
stability of carbonate and fluoride
containing apatites. Caries Res. 1983;
: 419ă429.
. Baig AA, Fox JL, Young RA, Wang Z,
Hsu J, Higuchi WI, et al. Relationships
among carbonated apatite solubility,
crystallite size, and microstrain
parameters. Calcif Tissue Int. 1999; 64:
ă49.
. Ito A, LeGeros RZ. Magnesiumă and
Zinc-substituted beta-Tricalcium
Phosphate Materials. In: Progress in
Bioceramics, Vallet-Regi M (Ed). Key
Engineer Mater. 2008; 377: 85ă98.
Trans Tech Publications, Zurich.