Biomedical subjects

L Tornvig

Publications and source records attributed to L Tornvig.

3 recordsLinked to original sources

PubMed2001

Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice.

Aging is associated with decreased trabecular bone mass and increased adipocyte formation in bone marrow. As osteoblasts and adipocytes share common precursor cells present in the bone marrow stroma, it has been proposed that an inverse relationship exists between adipocyte and osteoblast differentiation. In order to test this hypothesis, we studied mice treated with troglitazone (n = 9) given as a 0.2% of food admixture (2.0 g troglitazone per kg food) for 10 months and control mice (n = 9). Troglitazone is a potent stimulator of adipogenesis acting at the nuclear receptor: peroxisome proliferator activated receptor-gamma (PPARgamma). Histomorphometric analysis of proximal tibia was performed in order to quantitate the amount of trabecular bone volume per total volume (BV/TV %), adipose tissue volume per total volume (AV/TV %), and hematopoietic marrow volume per total volume (HV/TV %) using the point-counting technique. Bone size did not differ between the two groups. In troglitazone-treated mice, AV/TV was significantly higher than in control mice (4.7+/-2.1% vs. 0.2+/-0.3%, respectively, mean +/- SD, P < 0.001). BV/TV was similar in the two groups (16.9+/-5.6% for troglitazone-treated group vs. 14.9+/-4.7% for control group) as well as ash weight of the vertebrae. HV/TV was reduced in troglitazone-treated mice compared with control mice (78.4+/-6.8% vs. 84.9+/-4.7%, respectively, P < 0.05) and the presence of vascular sinusoids was reduced (7.3+/-1.7% vs. 16.1+/-5.6%, respectively, P < 0.05). Our data demonstrate that adipogenesis and osteogenesis can be regulated independently. Troglitazone-induced adipogenesis in the bone marrow may be caused by changes in the bone marrow vascularity.

Adipocytes↗

PubMed2000

Parathyroid hormone and growth hormone have additive or synergetic effect when used as intervention treatment in ovariectomized rats with established osteopenia.

The severely osteoporotic human skeleton is characterized by thin cortices and a very fragile cancellous framework. To increase the biomechanical competence of such a skeleton, powerful anabolic agents are needed. The aim of the present study was to compare the effect of parathyroid hormone (PTH), growth hormone (GH) and combination treatment with PTH and GH in an aged, rat model with established osteopenia. Furthermore, envelope- and site-specific effects of the two agents are described. Twelve-month-old virgin F344 rats were divided into six groups with 11 animals per group: (1) baseline; (2) sham-operated + solvent vehicle (s.v.) (sham); (3) ovariectomized + s.v. (ovx); (4) ovx + GH 2.5 mg/kg body weight per day; (5) ovx + PTH 80 microg/kg body weight per day; and (6) ovx + GH and PTH treatment. Group 1 were killed to establish baseline values. Groups 2 (sham) and 3 (ovx) were killed after 24 weeks. Groups 4, 5, and 6 were allowed to develop osteopenia for 16 weeks before treatment was initiated. Treatment was given for a period of 8 weeks. The effects of GH, PTH, and GH + PTH cotherapy were measured by biomechanical testing at four different skeletal sites: lumbar vertebra; femoral diaphysis; femoral neck; and distal femoral metaphysis. In addition, static histomorphometry was performed at the middiaphyseal region. Ovx induced a loss of bone strength at all sites, but this was significant only at the femoral diaphysis and distal metaphysis. GH could reverse the loss of strength at the diaphysis, but not at the metaphysis. PTH, on the other hand, reversed the loss of strength to values significantly over ovx at all four sites. At the metaphysis, PTH monotherapy increased strength to above sham levels. However, GH + PTH cotherapy showed additive or synergistic effects at the four tested sites, leading to strength values significantly over sham at all these sites. Static histomorphometry showed that GH exerted its main effect on the periosteal envelope and PTH on the endocortical envelope; for this reason, the GH + PTH combination treatment had an additive or synergistic effect. We conclude that GH and PTH have a very pronounced anabolic effect when given in cotherapy. Therefore, this treatment regime seems promising in the clinical situation for management of patients with severe, established osteoporosis.

Animals↗

PubMed2000

Trabecular bone structure and strength - remodelling and repair.

The strength of the spinal trabecular bone declines by a factor of 4-5 from the age of 20 to 80 years. At the same time, the volumetric (apparent) density declines by a factor of only 2. This discrepancy can be explained by the known power relationship between density and strength; this power relationship is based on the fact that trabecular bone is a porous material. To date, it has not been possible to determine or quantify the influence other factors may have in determining the strength of a loadbearing trabecular network. However, it is known that with age: 1) There is a loss of connectivity through osteoclastic perforations of horizontal struts. 2) There is an increase in anisotropy - again due to loss of horizontal struts, and perhaps also due to micro-modelling drift or to thickening of some vertical trabeculae. 3) The changes in the network can lead to the slenderness ratio between vertical and horizontal struts reaching a certain magnitude and thereby inducing buckling under compression. 4) Microdamage and microfractures will occur - mainly in these very loaded vertical struts. The microfractures will be repaired by microcallus formation, and these calluses will later be removed by the remodelling process. 5) Bone material quality will slightly change, leading to a decrease in collagen content and a relative increase in the degree of mineralisation. But, it is not known how these factors will influence the power relationship between density and strength. Nor is it known how different treatment regimens will affect the 'natural' power relationship: will the same curve be followed, but in the opposite direction? Or will the curve be less or more steep? Will the gain in bone strength be larger if treatment is started early - on the steep part of the curve? Furthermore, as trabecular bone can never be isolated in vivo, other factors need to be investigated: The interplay between the cortical shell and the trabecular network; transmission of load; the interplay between soft tissues (cartilage, connective tissue, muscle) and bone; the shock absorbing capacity of the discs; and the hydraulic effect of the bone marrow. In order to answer these questions, more in vitro and in vivo studies on human bone in relation to aging, to immobilisation, to exercise and in relation to different treatment regimens are needed.

Journal Article↗