Periapical bone resorption occurs following infection of the dental pulp and is mediated mainly by IL-1α in the murine model. The production and activity of IL-1α is modulated by a network of regulatory cytokines, including those produced by Th1 (pro-inflammatory) and Th2 (anti-inflammatory) subset T cells. This study was designed to assess the functional role of the Th2-type cytokines IL-4 and IL-10 in infection-stimulated bone resorption in vivo. The dental pulps of the first molars were exposed and infected with a mixture of four common endodontic pathogens, and bone destruction was determined by micro-computed tomography at sacrifice on day 21. The results demonstrate that IL-10−/− mice had significantly greater infection-stimulated bone resorption in vivo compared with wild-type mice (p < 0.001), whereas IL-4−/− exhibited no increased resorption. IL-10−/− had markedly elevated IL-1α production within periapical inflammatory tissues (>10-fold) compared with wild type (p < 0.01), whereas IL-4−/− exhibited decreased IL-1α production (p < 0.05). IL-10 also suppressed IL-1α production by macrophages in a dose-dependent fashion in vitro, whereas IL-4 had weak and variable effects. We conclude that IL-10, but not IL-4, is an important endogenous suppressor of infection-stimulated bone resorption in vivo, likely acting via inhibition of IL-1α expression.

Despite having a slightly larger trabecular bone compartment, C3H progenitors had dramatically lower vertebral trabecular BV/TV (-53%) and Tb.N (-40%) and higher Tb.Sp (71%) compared with B6 progenitors (p < 0.001 for all). Genome-wide quantitative trait analysis revealed a pattern of genetic regulation derived from 13 autosomes, with 5-13 quantitative trait loci (QTLs) associated with each of the vertebral trabecular bone traits, exhibiting adjusted LOD scores ranging from 3.1 to 14.4. The variance explained in the F2 population by each of the individual QTL after adjusting for contributions from other QTLs ranged from 0.8% to 5.9%. Taken together, the QTLs explained 22-33% of the variance of the vertebral traits in the F2 population. In conclusion, we observed a complex pattern of genetic regulation for vertebral trabecular bone volume fraction and microarchitecture using the F2 intercross of the C57BL/6J and C3H/HeJ inbred mouse strains and identified a number of QTLs, some of which are distinct from those that were previously identified for total femoral and vertebral BMD. Identification of genes that regulate trabecular bone traits may ultimately yield important information regarding the mechanisms that regulate the acquisition and maintenance of mechanical integrity of the skeleton.

The experimental work characterizing the anabolic effect of parathyroid hormone (PTH) in bone has been performed in nonmurine ovariectomized (OVX) animals, mainly rats. A major drawback of these animal models is their inaccessibility to genetic manipulations such as gene knockout and overexpression. Therefore, this study on PTH anabolic activity was carried out in OVX mice that can be manipulated genetically in future studies. Adult Swiss-Webster mice were OVX, and after the fifth postoperative week were treated intermittently with human PTH(1-34) [hPTH(1-34)] or vehicle for 4 weeks. Femoral bones were evaluated by microcomputed tomography (CT) followed by histomorphometry. A tight correlation was observed between trabecular density (BV/TV) determinations made by both methods. The BV/TV showed >60% loss in the distal metaphysis in 5-week and 9-week post-OVX, non-PTH-treated animals. PTH induced a ϳ35% recovery of this loss and a ϳ40% reversal of the associated decreases in trabecular number (Tb.N) and connectivity. PTH also caused a shift from single to double calcein-labeled trabecular surfaces, a significant enhancement in the mineralizing perimeter and a respective 2-and 3-fold stimulation of the mineral appositional rate (MAR) and bone formation rate (BFR). Diaphyseal endosteal cortical MAR and thickness also were increased with a high correlation between these parameters. These data show that OVX osteoporotic mice respond to PTH by increased osteoblast activity and the consequent restoration of trabecular network. The SwissWebster mouse model will be useful in future studies investigating molecular mechanisms involved in the pathogenesis and treatment of osteoporosis, including the mechanisms of action of known and future bone antiresorptive and anabolic agents.

Recently, an imaging technique using microcomputed tomography (micro-CT) has emerged as a method for nondestructively assessing the microarchitecture of unprocessed surgical bone biopsy specimens. Using micro-CT, two-dimensional (2D) axial images were obtained from undecalcified transiliac bone biopsies which were taken from 15 patients with various metabolic bone diseases. Total area, bone area, and bone perimeter were determined, from which the bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated semiautomatically and instantaneously. To evaluate the validity of this technique as a useful tool, the results were compared with those obtained from conventional histomorphometry. There were significant correlations between the two techniques for all parameters, with correlation coefficients ranging from 0.759 (Tb.N, P < 0.005) to 0.949 (BV/TV, P < 0.0001). Different resolutions seem to lead to major differences in perimeter values measured by the two methods. These factors may explain why the correlation coefficients of Tb.N and Tb.Th estimated from the perimeter and area is lower than that of BV/TV. Our results show that the micro-CT based on 2D images is a useful tool for imaging and nondestructively quantifying the microarchitecture of trabecular bone in unprocessed surgical bone specimens.

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The purpose of this study was to use histomorphometry to compare the microstructure of trabecular and cortical bone in patients with primary hyperparathyroidism (PH) with that seen in osteoporosis. Histomorphometric and node-strut analyses of iliac bones were performed on 11 female patients with PH (61.3 +/- 8.0 years old) and 61 age-matched female patients with involutional osteoporosis (OP) (63.6 +/- 5.6 years old). Cancellous bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and wall thickness (W.Th) were not significantly different in these two groups. The bone formation rate (BFR) tended to be higher in the PH group than in the OP group. The number of nodes (N.Nd/TV) and node-to-node strut length (Nd.Nd/TV) were significantly higher in the PH group than in the OP group. The number of termini (N.Tm/TV) and terminus-to-terminus strut length/total strut length (Tm.Tm/TSL) were significantly lower in the PH group; cortical porosity was significantly higher in the PH group than in the OP group. No correlation was found between age and N.Nd in the PH group, but there was a negative correlation between age and N.Nd in the OP group. Our results show that trabecular connectivity was maintained while cortical porosity deteriorated in patients with PH compared with OP. These results suggest that there are microstructural differences between PH and OP in cancellous and cortical bone that result from the bone remodeling sequence in humans.

Peripheral quantitative computed tomography (pQCT) is able to evaluate trabecular and cortical bone separately, and to determine geometric properties from cross-sectional images for noninvasive assessments of mechanical strength. In order to assess the diagnostic value of pQCT of the femoral neck, 60 healthy women were examined with a new pQCT machine, XCT-3000 (Norland-Stratec, Germany), which is suitable for direct measurement of the hip. The region of interest chosen was the center of the femoral neck. pQCT of the distal radius and dual energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck were also performed. The study demonstrated that total bone mineral density (BMD) (femoral MD) and trabecular BMD (femoral-TBD) decreased with advancing age. Percent cortical area showed a small but significant decrease with advancing age and % trabecular area increased slightly. Both the endosteal perimeter and the periosteal perimeter were relatively constant with aging. Bone strength index (BSI) and stress-strain index (SSI), which reflect the mechanical strength of bone, declined with advancing age, especially after menopause. Femoral TBD correlated strongly with femoral neck BMD by DXA and L2-L4 BMD by DXA but femoral-CBD did not correlate with femoral neck BMD by DXA. Volumetric BMD of the femoral neck and distal radius were closely correlated. It is concluded that (1) cortical thinning occurs with aging by endocortical resorption and loss of femoral-TBD; (2) loss of femoral-CBD occurred at a slower rate than radial CBD, perhaps due to the weight-bearing effect; (3) biomechanical parameters such as the BSI and SSI may reflect increasing fragility of the femoral neck in pre- and postmenopausal women; (4) pQCT of the femoral neck had diagnostic value at least equivalent to that of DXA or pQCT of the distal radius.

We reviewed 110 trigger digits, treated surgically, to compare the outcomes of trigger finger and trigger thumb in terms of peri-operative characteristics and complications. The patients with trigger thumb complained mainly of pain on motion, while those with trigger finger complained of triggering or limited range of motion. Trigger fingers had a significantly longer duration before surgery than did trigger thumbs. Trigger fingers took significantly longer for the symptoms to subside. In our series, 64% of trigger fingers had a flexion contracture of the PIP joint more than three weeks after surgery. Our results suggest that the peri-operative characteristics and outcomes differ between trigger finger and thumb, and that the surgical outcome for trigger finger was poorer than that for trigger thumb, partly due to flexion contracture of the PIP joint.