Increasing Osteoblast numbers & fighting osteoporosis

[Guest guest]

Three interesting papers showing how Vit D, GH/IGF-1 & Arginine/Lysine can help

to boost falling osteoblast numbers.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

1285997 & dopt=Abstract

Rheum Dis Clin North Am 2001 Feb;27(1):215-33,

Emerging anabolic treatments for osteoporosis.

Rosen CJ, Rackoff PJ.

Maine Center for Osteoporosis Research and Education, St ph Hospital,

Bangor, USA. rofe@...

Therapy for osteoporosis is principally centered on the use of agents that block

bone resorption and supplementation

with vitamin D and calcium.

Although these drugs are effective in reducing the risk of subsequent fractures,

and modestly increasing bone density,

most patients being treated for osteoporosis still have low bone mass and a

greater risk of fracture.

Anabolic agents stimulate bone formation, strength, and mass. In addition,

there is emerging evidence that anabolic

agents can reduce subsequent fracture risk.

The two most promising agents, parathyroid hormone (PTH) and GH/IGF-I, act to

increase osteoblast mediated bone

formation.

A review of the potential usefulness of PTH and GH/IGF-I is presented.

PMID: 11285997 [PubMed - in process]

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

1393808 & dopt=Abstract

Biomed Pharmacother 2001 May;55(4):213-20

Effect of L-lysine and L-arginine on primary osteoblast cultures from normal and

osteopenic rats.

Fini M, Torricelli P, Giavaresi G, Carpi A, Nicolini A, Giardino R.

Experimental Surgery Department, Research Institute Codivilla-Putti, Rizzoli

Orthopaedic Institute, Bologna, Italy.

milena.fini@...

A therapeutic role of amino acids L-lysine (Lys) and L-arginine (Arg) in

osteoporosis and fracture healing was

demonstrated previously by in vivo studies.

In the present study, primary cultures of osteoblasts were used to investigate

the effect of amino acids on gene

expression (alkaline phosphatase activity, ALP; osteocalcin, OC; type I

collagen), nitric oxide production (NO) and

proliferation (MTT) of cells.

Cells were isolated from the distal femurs of normal and osteopenic rats.

Normal and osteopenic bone-derived cells were divided into four groups: control,

Lys (0.587 mg/mL/d), Arg (0.625

mg/mL/d), and Lys + Arg (0.587 + 0.625 mg/mL/d).

No evidence of differences between normal and osteopenic bone-derived cultures

in basal conditions was observed.

A significant (P = 0.002) increase of 10.4% in NO production was observed in

normal bone-derived osteoblasts treated

with Lys + Arg when compared to the control group at 7 days.

At the same time, normal bone-derived osteoblasts treated with Arg and Lys + Arg

showed significant increases in type I

collagen synthesis of 25.3% and 28.4%, respectively, when compared to the

control group.

Osteopenic bone-derived osteoblasts showed significant (P = 0.002) increases of

27.6% in MTT and 28.7% in cell count at

48 hours when treated with Lys + Arg in comparison with the control group.

At 7 days, NO production and type I collagen synthesis increased significantly

(P< 0.005) both in osteopenic

bone-derived osteoblasts treated with Arg (NO: 18.5%; type I collagen: 34.4%)

and Lys + Arg (NO: 23.7%; type I collagen:

20.9%) compared to the control group.

Finally, a significant (P = 0.025) decrease of 5.8% in OC level was observed in

osteopenic bone-derived osteoblasts

treated with Arg.

Results suggest that the potential therapeutic effect of Lys and Arg on bone

could be related, at least in part, to an

improvement of NO production and type I collagen synthesis by osteoblasts both

in normal and in osteopenic bone.

In osteopenic bone-derived osteoblasts this synthetic phase is preceded by an

initial increase of cell proliferation.

PMID: 11393808 [PubMed - in process]

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

1358669 & dopt=Abstract

J Steroid Biochem Mol Biol 2001 Apr;77(1):1-11

Vitamin D compounds exert anti-apoptotic effects in human osteosarcoma cells in

vitro.

Hansen CM, Hansen D, Holm PK, Binderup L.

Department of Biochemistry, Leo Pharmaceutical Products, Industriparken 55,

DK-2750, Ballerup, Denmark

Several studies have demonstrated that vitamin D regulates growth and

differentiation in bone cells in vitro.

In addition, in vivo studies have shown that vitamin D stimulates bone

formation, increases the number of osteoblast

precursor cells and prevents bone mineral loss.

These observations indicate that vitamin D may have anabolic effects on bone,

and thus therapeutic potential in the

treatment of osteoporosis.

However, little is known about the effects of vitamin D on apoptosis in bone

cells and about the contribution of this

process to the effect of vitamin D on bone mineral loss.

To investigate this aspect in more detail, we studied the effect of

1alpha,25(OH)(2)D(3) and a series of analogues on

apoptosis in human osteosarcoma cells.

No significant induction of apoptosis was observed with any of the compounds

after a 5 day treatment period. In

contrast, some of the analogues showed a tendency to protect the cells from

undergoing apoptosis.

This anti-apoptotic effect of vitamin D was further confirmed by the ability of

1alpha,25(OH)(2)D(3) to suppress

camptothecin- and staurosporin-induced DNA fragmentation in the cells.

In cultures treated simultaneously with 1alpha,25(OH)(2)D(3) in combination with

camptothecin or staurosporin, the level

of DNA fragmentation was markedly reduced compared with cultures treated with

camptothecin or staurosporin alone.

On the basis of the present results, it is therefore concluded that vitamin D

displays anti-apoptotic effects in human

osteoblast-like osteosarcoma cells in vitro.

This observation suggests that besides regulating growth and differentiation,

vitamin D exerts its anabolic effects on

bone by protecting osteoblastic cells from undergoing apoptosis.

PMID: 11358669 [PubMed - in process]

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Good Health & Long Life,

Greg ,

http://www.ozemail.com.au/~gowatson

gowatson@...