Inflammation-mediated Osteopenia Research Articles

Effects of alpha-Lipoic Acid on Bone Metabolism in Rats with Low Bone Mass

Background: Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. In our previous study, α-lipoic acid (α-LA), a thiol antioxidant, suppressed both osteoclastogenesis and bone resorption, and also prevented TNF-α-induced apoptosis of osteoblast lineages. The effects of α-LA were investigated on bone metabolism in rats with a low bone mass. Methods: An ovariectomy (OVX) or Talc injection (inflammation-mediated osteopenia, IMO) was performed in 12 week old female Sprague-Dawley rats. Diets cont aining either 0.3%, 0.5% or 1.0% α-LA were administered to the OVX rats for 16 weeks, and to the IMO rats for 21 days. The bone mineral densities (BMD) of the anterior-posterior lumbar spine and total femur were measured using dual-energy X-ray absorptiometry (Hologic QDR 4500-A), with small animal software. The plasma bone specific alkaline phosphatase activity (BSAP) and urinary free deoxypyridinoline concentration (DPD) were determined using enzyme immunoassay methods. Results: The body weights were significantly decreased in the OVX rats on the diets containing 0.3 and 0.5% α-LA than in the OVX control. No significant differences in the BMD at either site were noted between rats administered the diets with or without α-LA. However, the administration of various doses of α-LA noticeably decreased the level of urinary DPD in both the OVX a nd IMO rats. High doses of α-LA (0.5% and/or 1.0%) also decreased the levels of plasma BSAP in both models. Conclusion: Although no increase in BMD was demonstrated by the administration of α-LA, these results suggest that α-LA suppresses the rates of bone turnover in rats with a low bone mass (J Kor Soc Endocrinol 20:476～487, 2005).

Genetic determinants of IL-6 expression levels do not influence bone loss in inflammatory bowel disease.

Bone loss in inflammatory bowel disease (IBD) is presumed to be mediated by inflammation. Increased levels of the multifunctional cytokine IL-6 in inflammatory diseases have been proposed to be the link in such "inflammation-mediated osteopenia." A recently described G/C polymorphism with an effect on transcription rate and plasma levels of IL-6 suggests a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals. This study aimed to assess the frequency of genotypes and haplotypes of the G/C polymorphism of IL-6 in IBD patients. A further aim was to assess whether carriage of the potentially protective CC genotype is favorable with respect to the development of bone disease in IBD. The IL-6 polymorphism was typed in 105 IBD patients and 113 healthy controls. Bone mineral density was evaluated at baseline and after a prospective 2-year-follow-up. The favorable CC genotype with decreased IL-6 release was not underrepresented in IBD patients compared to healthy controls. Carriage of this genotype was not protective with respect to the development of bone disease, either for the bone mineral density at baseline or for the prospectively observed bone loss. Within the subgroup of patients who did not receive steroids during follow-up, the prospectively observed bone loss was even slightly higher in CC carriers, but differences did not reach significance. Genetically determined differences in the degree of the IL-6 response to stressful stimuli are no major predictors for the degree of bone disease in IBD patients.

Inflammation mediated osteopenia (IMO): therapeutic effect of D-hormone and the role of cytokines

Inflammation-mediated osteopenia is an animal model for bone mass reduction following chronic inflammation. We found a reduction of calcitriol serum concentrations during the inflammatory process, in addition cytokines are increased. Treatment of the animals with calcitriol is able to prevent bone mass reduction and to preserve bone formation.

Quantitative analysis of three-dimensional complexity and connectivity changes in trabecular microarchitecture in relation to aging, menopause, and inflammation

There are several types of bone loss besides that associated with normal aging, eg, that associated with the menopause, and that associated with chronic inflammation, and these are considered to be caused by different mechanisms. The microarchitecture that results from these different bone-loss mechanisms would not be the same. The purpose of this study was to investigate differences in the three-dimensional trabecular microarchitecture in various types of osteopenia, using microcomputed tomography (Micro-CT). Thirty-five Fisher 344 rats were divided into five groups (control, young, senile, ovariectomized [OVX], and inflammation-mediated osteopenia [IMO]) and distal femoral metaphysis was scanned by Micro-CT to nondestructively acquire a 3-D CT stack consisting of 50 consecutive slices at a spatial resolution of 26μm. The volume of interest, consisting of the secondary spongiosa, was prepared to analyze the 3-D trabecular microarchitecture. A parametric analysis was carried out using bone volume fractions, fractal dimensions, and the first Betti number in order to quantitatively express the mass, complexity, and connectivity of the trabecular microarchitecture. Complexity tended to decrease with age, and decreased significantly in estrogen deficiency-induced and inflammation-mediated osteopenia. Connectivity did not appear to change with aging, but was significantly decreased in estrogen deficiency-induced and inflammation-mediated osteopenia. There was no significant difference between the OVX and the IMO groups.

Influence of inflammation-mediated osteopenia on the regional acceleratory phenomenon and the systemic acceleratory phenomenon during healing of a bone defect in the rat.

We have previously shown that restoration of a local bone defect in the rat not only leads to a regional acceleratory phenomenon (RAP), but also to a systemic acceleration of osteogenesis (SAP) at distant sites of the skeleton. In this study, we investigated whether specific inhibition of osteoblasts would affect the local RAP and the systemic acceleratory phenomenon (SAP) healing sites. Systemic inhibition of osteoblasts was induced by inflammation-mediated osteopenia (IMO), a nonspecific type of inflammation initiated by s.c. injections of sterile talc. A drill hole defect 1.2 mm in diameter was performed at the midshaft of the left tibia of female rats. On day 7, during the formation phase of the local healing process, IMO did not influence the number of osteoblasts or the bone volume in the marrow cavity of the local healing site, whereas it did lead to a significant reduction of osteoblast number and bone volume at the systemic site (subepiphyseal spongiosa of the tibia). By contrast, on days 14 and 21, during the resorption phase of bone healing. IMO led to a significant reduction in both osteoblast number and bone volume in the marrow cavity of the local healing site. At the same time, however, it did not influence the cortical area of the bone defect where newly formed bone is needed to ensure mechanical stability. In summary, our model of bone healing reveals that a humoral noxious osteoblast stimulus such as IMO is able to inhibit systemically osteoblasts stimulated by SAP, whereas it is not able to inhibit osteoblasts either from producing woven bone during a RAP or from producing bone that is needed to mechanically stabilize a defect.

The Influence of Inflammation-Mediated Osteopenia (IMO) on the Structure of Rabbit Bone and Skin Collagen Fibrils

The influence of Inflammation Mediated Osteopenia (IMO) on rabbit skin and bone (trabecular and cortical) collagen fibrils was studied by electron microscopy. Severe abnormalities in collagen fibril structure were detected, at the ultrastructural level, in skin and bone specimens from IMO rabbits. In treated animals the arrangement of fibrils is anarchic. The overall collagen fibril architecture is disturbed compared to normal. IMO collagen fibrils' mean diameter values were significantly larger than those from controls, in all examined tissues. However, the banding patterns of fibrils were normal in all cases. Computer analysis shows no differences in charged amino acid composition between IMO and untreated samples. Our results show a correlation between the effects induced by osteopenia on skin and bone collagen.

Maxillary Sinus Atelectasis

Two patients are presented with maxillary bone loss and atelectasis of the sinus walls in association with chronic subclinical maxillary sinusitis. Maxillary sinus atelectasis results in a mild cosmetic deformity, but may also cause diplopia by involving the orbital floor. Ostial obstruction and inflammation-mediated osteopenia are postulated to be the responsible mechanisms. Surgical treatment of the sinusitis may prevent progression of the bone loss.

Effects of endogenous and exogenous calcitonin on inflammation-mediated osteopenia in the rat.

Inflammation-mediated osteopenia (IMO) in the rat is characterized by loss of bone mass within 3 weeks after induction of nonspecific inflammation (s.c. talcum injections) in growing rats. Histologically, this shows as marked inhibition of osteoblasts 3 days after the initiation of IMO. The role of calcitonin (CT) was investigated in the present study. A reversible increase of serum CT levels was found after intraperitoneal calcium challenge in rats on day 4 after induction of IMO, which was thought to be a result from calcium efflux from bone. No difference in stimulated serum CT levels between the rats with and without IMO was seen on any other day during 4 weeks after initiation of IMO. Bone loss after IMO was more pronounced in normocalcemic and euthyroid rats with deficiency of endogenous CT (thyroidectomy with parathyroid gland reimplanted) (-12.9%) compared with sham operated controls with IMO (-3.25%). Daily subcutaneous injections of 100 mIU salmon CT in rats with and without IMO did not prevent the development of bone loss. This might have been due to the growing state of rats of this age group. Our results support the hypothesis that endogenous CT physiologically has a bone protective role. They furthermore are consistent with the view that endogenous CT itself is not pathogenetically involved in the development of osteoporosis.

Inflammation-mediated osteopenia (IMO): No change in bone resorption during its development

Inflammation-mediated osteopenia (IMO): No change in bone resorption during its development

Effect of HEBP (1-hydroxyethylidene-1, 1-bisphosphonic acid) on inflammation-mediated osteopenia in the rat

Trabecular bone volume of rat leg bones decreased following the subcutaneous injection of talcum (magnesium silicate). The effect of HEBP (1-hydroxyethylidene -1, 1-bisphosphonic acid) on this osteopenia was investigated.

1,25-dihydroxyvitamin D 3 prevents the decrease of bone mineral appositional rate in rats with inflammation-mediated osteopenia (IMO)

We have studied the effects of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) on bone mass and bone mineral appositional rate in intact rats and rats with inflammation-mediated osteopenia (IMO), where osteoblast number and mineral appositional rate are decreased. 1,25(OH) 2D 3 prevents IMO-specific bone loss when given in a daily dose of 25 ng per rat, but does not when given in higher doses. The hormone was effective, when given over the complete duration of the experiment (21 days), but not when given over shorter time periods (7 and 14 days, respectively). 1,25(OH) 2D 3 prevents IMO-dependent reduction in mineral appositional rate and leads to an only moderate increase in intact rats. We conclude, that 1,25(OH) 2D 3 is more effective in stimulating mineral appositional rate in rats with IMO where mineral apposition is impaired.

Effects of ovariectomy on inflammation-mediated osteopenia (IMO)

Effects of ovariectomy on inflammation-mediated osteopenia (IMO)

Inflammation-mediated osteopenia: bone loss is not due to osteoclast activation

Inflammation-mediated osteopenia: bone loss is not due to osteoclast activation

Inflammation-mediated osteopenia (IMO) during acute inflammation in rats is due to a transient inhibition of bone formation.

Local inflammation was induced in rats through the subcutaneous injection of magnesium silicate. Trabecular bone volume of the tibia decreased progressively during a 3 week observation period following the inflammatory stimulus. The trabecular bone surface covered with osteoblasts was strikingly reduced during the first week but had normalized by the end of the third week. Calcification rate in the cortical bone of the tibia was reduced with a parallel reduction in endosteal osteoid seam width. Both calcification rate and tetracycline double-labeled surface of vertebral trabecular bone were reduced during the first 2 weeks. Neither total bone resorption surface nor active bone resorption surface were increased. There was a decrease in osteoclast numbers/mm2 bone tissue associated with decreasing bone volume. Our data demonstrate a transient inhibition of bone formation during acute inflammation in the rat and indicate that changes in osteoblast function are part of the acute phase response following local inflammation.

Intestinal calcium absorption causes the rise in serum calcium in parathyroidectomized rats with "inflammation-mediated osteopenia" (IMO)

Intestinal calcium absorption causes the rise in serum calcium in parathyroidectomized rats with "inflammation-mediated osteopenia" (IMO)

Inflammation-mediated osteopenia in the rat: The effects of artificial granuloma and sham operation on cortical and trabecular bone

Recent studies have established that generalized loss of trabecular bone occurs in the growing rat following day-to-day inflammatory irritation for a period of 3 wk. We can now demonstrate that there are similar effects on bone in milder but more prolonged chronic inflammation (14 wk). Thus, there were significant decreases in trabecular bone mass as well as in cortical bone after weekly subcutaneous injections or implantations of nonspecific irritants. Osteopenia, induced by a single but extensive inflammatory lesion, remained apparent even 14 wk after induction. This indicates that inflammation-mediated osteopenia is at least incompletely reversible. A less pronounced but similar reduction of cortical and trabecular bone was observed in rats following sham operation. This might be of importance in all animal studies on bone metabolism that include surgical procedures.

Non-specific inflammation corrects PTX dependent hypocalcemia and leads to inflammation mediated osteopenia (IMO)

Non-specific inflammation corrects PTX dependent hypocalcemia and leads to inflammation mediated osteopenia (IMO)

Exclusion of autonomous 1,25(OH)2Vitamin D3 (calcitriol) formation as a pathogenetic principle of inflammation-mediated osteopenia (IMO)

Exclusion of autonomous 1,25(OH)2Vitamin D3 (calcitriol) formation as a pathogenetic principle of inflammation-mediated osteopenia (IMO)

Inflammation-mediated osteopenia in the rat: a new animal model for pathological loss of bone mass.

We have developed a rat model of inflammation-mediated osteopenia. Generalized loss of trabecular bone occurs in the rat after sc injection of nonspecific irritants such as talcum (magnesium silicate) and cotton wool (Cellulose). Although it appears likely that a systemic mediator of bone resorption is responsible for these effects, the loss of bone was not due to increased PTH secretion, since it occurred in parathyroidectomized rats, nor due to excessive 1,25-dihydroxyvitamin-D3 production. In parathyroidectomized rats, this inflammation was associated with significant increase in serum calcium within 4-7 days independent of its cause. Identification and characterization of this mechanism may provide insight into the bone loss associated with chronic inflammatory diseases such as rheumatoid arthritis and periodontal disease.