Irregular Contour of Inner Ear Structures and Hypomineralized Areas at Otic Capsule: Are They Other Additional Imaging Findings of Incomplete Partition-III?

PURPOSE: Incomplete partition III (IP-III) characterized by congenital mixed or sensorineural hearing loss is a rare genetic disease transmitted through X-linked inheritance. Incomplete partition III can be easily achieved based on pathognomonic computed tomography findings. The aims of this study were to investigate the otic capsule abnormalities in IP-III and to report irregular contour of membranous labyrinth and hypomineralized areas at otic capsule, which have not previously been described. MATERIALS AND METHODS: The otic capsule features of 10 subjects (8 affected patients, 1 of whom is a female; 2 carrier mothers), who were diagnosed on clinical and typical radiologic findings, were analyzed. RESULTS: All patients had typical IP-III as described in the literature. Seven of 10 patients had irregular contour. Seven of 10 patients demonstrated hypomineralized areas, which were very hypodense to normally develop otic capsule areas. One affected patients and 2 carrier mothers had a normal-looking membranous labyrinth contour and normal mineralization at otic capsule. CONCLUSIONS: We report for the first time the irregular contour of inner ear structures and hypodense otic capsule areas in patients with IP-III. We think that though speculative, abnormal development of the inner endosteal layer results in irregular contour of inner ear structures. Hypomineralized areas at otic capsule could be explained by abnormal development of middle enchondral layer due to reduced or absent vascular supply from middle ear mucosa during fetal life. These findings may be accepted as additional criteria of IP-III.

RANKL cytokine enhances TNF-induced osteoclastogenesis independently of TNF receptor associated factor (TRAF) 6 by degrading TRAF3 in osteoclast precursors.

Cytokines, including receptor activator of nuclear factor κB ligand (RANKL) and TNF, induce increased osteoclast (OC) formation and bone loss in postmenopausal osteoporosis and inflammatory arthritides. RANKL and TNF can independently induce OC formation in vitro from WT OC precursors via TNF receptor-associated factor (TRAF) adaptor proteins, which bind to their receptors. Of these, only TRAF6 is required for RANKL-induced osteoclastogenesis in vitro However, the molecular mechanisms involved remain incompletely understood. Here we report that RANKL induced the formation of bone-resorbing OCs from TRAF6-/- OC precursors when cultured on bone slices but not on plastic. The mechanisms involved increased TNF production by TRAF6-/- OC precursors resulting from their interaction with bone matrix and release of active TGFß from the resorbed bone, coupled with RANKL-induced autophagolysosomal degradation of TRAF3, a known inhibitor of OC formation. Consistent with these findings, RANKL enhanced TNF-induced OC formation from TRAF6-/- OC precursors. Moreover, TNF induced significantly more OCs from mice with TRAF3 conditionally deleted in myeloid lineage cells, and it did not inhibit RANKL-induced OC formation from these cells. TRAF6-/- OC precursors that overexpressed TRAF3 or were treated with the autophagolysosome inhibitor chloroquine formed significantly fewer OCs in response to TNF alone or in combination with RANKL. We conclude that RANKL can enhance TNF-induced OC formation independently of TRAF6 by degrading TRAF3. These findings suggest that preventing TRAF3 degradation with drugs like chloroquine could reduce excessive OC formation in diseases in which bone resorption is increased in response to elevated production of these cytokines.

In vitro evaluation of adhesion/proliferation of human gingival fibroblasts on demineralized root surfaces by toluidine blue O in antimicrobial photodynamic therapy.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) in Dentistry has important effects as bacterial destruction in areas with periodontal disease. Some dyes applied in aPDT could present low pH and, consequently, result in tooth demineralization. This study evaluated demineralization produced by aPDT with toluidine blue O (TBO) at low pH and analyzed adhesion/proliferation of human gingival fibroblasts (HGF). METHODS: In the 1st phase, bovine enamel and root dentin fragments received 2 treatments: PDT4 group (TBO-100 µg/ml-pH 4-60s) plus laser (660 nm, 45 J/cm(2), 1.08 J, 30 mW, 30 s, spot 0.024 cm(2), 1.25 W/cm(2), sweeping, non-contact) and CA group (citric acid plus tetracycline-pH 1-180 s). Surface hardness loss and tooth wear were statistically analyzed (Student's t test, ANOVA/Tukey, p<0.05). In the 2nd phase, human dentin fragments were divided in C (control group-scaling and root planing), PDT4 and CA. HGF (10(4), 5th passage) were cultured on these fragments for 24, 48 and 72 h and counted in scanning electron microscopy photographs. Number of HGF was analyzed using repeated-measures ANOVA and Tukey (p<0.05). RESULTS: Percentage of surface hardness loss was similar in dentin for PDT4 (71.5%) and CA (76.1%) (p>0.05) and higher in enamel for CA (68.0%) compared to PDT4 (34.1%) (p<0.05). In respect to wear, no difference was found between PDT4 (dentin: 12.58 µm, enamel: 12.19 µm respectively) and CA (dentin: 11.74 µm and enamel: 11.03 µm) (p>0.05). Number of HGF was higher after 72 h in CA group (2.66, p<0.05) compared to PDT4 (2.2) and C (1.33). CONCLUSION: PDT4 is not as aggressive as CA for enamel. However, dentin demineralized promoted by PDT4 does not stimulate HGF adhesion and proliferation as CA.

Osteocyte-directed bone demineralization along canaliculi.

The mammalian skeleton stores calcium and phosphate ions in bone matrix. Osteocytes in osteocyte lacunae extend numerous dendrites into canaliculi less than a micron in diameter and which are distributed throughout bone matrix. Although osteoclasts are the primary bone-resorbing cells, osteocytes also reportedly dissolve hydroxyapatite at peri-lacunar bone matrix. However, robust three-dimensional evidence for peri-canalicular bone mineral dissolution has been lacking. Here we applied a previously reported Talbot-defocus multiscan tomography method for synchrotron X-ray microscopy and analyzed the degree of bone mineralization in mouse cortical bone around the lacuno-canalicular network, which is connected both to blood vessels and the peri- and endosteum. We detected cylindrical low mineral density regions spreading around canaliculi derived from a subset of osteocytes. Transmission electron microscopy revealed both intact and demineralized bone matrix around the canaliculus. Peri-canalicular low mineral density regions were also observed in osteopetrotic mice lacking osteoclasts, indicating that osteoclasts are dispensable for peri-canalicular demineralization. These data suggest demineralization can occur from within bone through the canalicular system, and that peri-canalicular demineralization occurs not uniformly but directed by individual osteocytes. Blockade of peri-canalicular demineralization may be a therapeutic strategy to increase bone mass and quality.

Truncated-correlation photothermal coherence tomography of artificially demineralized animal bones: two- and three-dimensional markers for mineral loss monitoring.

The challenge of depth-resolved, nonionizing (hybrid-optical) detection of mineral loss in bones is addressed using truncated-correlation photothermal coherence tomography (TC-PCT). This approach has importance not only in ground-based clinical procedures, but also in microgravity space applications. Analogous to x-ray morphometric parameters, two- and three-dimensional markers have been defined and estimated for chemically demineralized goat rib bones. Cortical and trabecular regions have been analyzed independently and together using the computational slicing advantage of TC-PCT, and the results have been verified using micro-CT imaging (the gold standard). For low-demineralization levels, both modalities follow the same trend. However, for very high mineral loss that is unlikely to occur naturally, anomalies exist in both methods. Demineralization tracking has been carried out to a depth of ∼3 mm below the irradiated surface. Compared with micro-CT imaging, TC-PCT offers an improved dynamic range, which is a beneficial feature while analyzing highly demineralized bones. Also, TC-PCT parameters are found to be more sensitive to trabecular and combined cortical-trabecular demineralization compared with x-ray parameters. Axial and lateral resolutions in bone imaging for the current instrumental configuration are ∼25 and 100 µm, respectively.

A study to evaluate the cause of bone demineralization in gynecological cancer survivors.

BACKGROUND: An association between treatment for gynecological cancers and risk of osteoporosis has never been formally evaluated. Women treated for these cancers are now living longer than ever before, and prevention of treatment-induced morbidities is important. We aimed to distinguish, in gynecological cancer survivors, whether cancer therapy has additional detrimental effects on bone health above those attributable to hormone withdrawal. METHODS: We performed a retrospective cross-sectional analysis of dual energy x-ray absorptiometry (DEXA) scan results from 105 women; 64 had undergone bilateral salpingo-oophorectomy (BSO) followed by chemotherapy or radiotherapy for gynecological malignancies, and 41 age-matched women had undergone BSO for benign etiologies. All were premenopausal prior to surgery. RESULTS: The median age at DEXA scan for the cancer group was 42 years, and 66% had received hormonal replacement therapy (HRT) following their cancer treatment. For the benign group, the median age was 40 years, and 87% had received HRT. Thirty-nine percent of cancer survivors had abnormal DEXA scan results compared to 15% of the control group, with the majority demonstrating osteopenia. The mean lumbar spine and femoral neck bone mineral densities (BMDs) were significantly lower in cancer patients. A history of gynecological cancer treatment was associated with significantly lower BMD in a multivariate logistic regression. CONCLUSIONS: Women treated for gynecological malignancies with surgery and adjuvant chemotherapy have significantly lower BMDs than age-matched women who have undergone oophorectomy for noncancer indications. Prospective evaluation of BMD in gynecological cancer patients is recommended to facilitate interventions that will reduce the risk of subsequent fragility fractures.

Risk factors for developing mineral bone disease in phenylketonuric patients.

There is a compromised bone mass in phenylketonuria patients compared with normal population, but the mechanisms responsible are still a matter of investigation. In addition, tetrahydrobiopterin therapy is a new option for a significant proportion of these patients and the prevalence of mineral bone disease (MBD) in these patients is unknown. We conducted a cross-sectional observational study including 43 phenylketonuric patients. Bone densitometry, nutritional assessment, physical activity questionnaire, biochemical parameters, and molecular study were performed in all patients. Patients were stratified by phenotype, age and type of treatment. The MBD prevalence in phenylketonuria was 14%. Osteopenic and osteoporotic (n=6 patients) had an average daily natural protein intake significantly lower than the remaining (n=37) patients with PKU (14.33 ± 8.95 g vs 21.25 ± 20.85 g). Besides, a lower body mass index was found. There were no statistical differences in physical activity level, calcium, phosphorus and fat intake, and in phenylalanine, vitamin D, paratohormone, docosahexaenoic and eicosapentaenoic acid blood levels. Mutational spectrum was found in up to 30 different PAH genotypes and no relationship was established among genotype and development of MBD. None of the twelve phenylketonuric patients treated with tetrahydrobiopterin (27.9%), for an average of 7.1 years, developed MBD. Natural protein intake and blood levels of eicosapentaenoic acid were significantly higher while calcium intake was lower in these patients. This study shows that the decrease in natural protein intake can play an important role in MBD development in phenylketonuric patients. Therapy with tetrahydrobiopterin allows a more relaxed protein diet, which is associated with better bone mass.

Corticosteroid exposure not associated with long-term bone mineral density in pediatric liver transplantation.

OBJECTIVES: The aim of the study was to examine the association of corticosteroid exposure and other skeletal risk factors with bone mineral density (BMD) and fractures following pediatric liver transplantation (LT) at a large single center. PATIENTS AND METHODS: Lumbar spine BMD, measured using dual-energy x-ray absorptiometry (DXA), was corrected for bone age in 52 ambulatory children ages 4 to 18 years, at least 1 year post-LT. Potential risk factors for skeletal health such as corticosteroid exposure, dietary and lifestyle factors, and growth and fracture occurrence, were related to BMD using univariate and multivariate regression analyses. RESULTS: The prevalence of low BMD (z score <-2) and post-LT fractures was 3 of 52 (5.8%) and 11 of 52 (21%), respectively. Univariate analysis revealed age >10 years at LT and body mass index (BMI) < 85th percentile at time of DXA were significantly associated with BMD (both P = 0.02). BMD did not correlate with corticosteroid dosage in the first year post-LT, the year before DXA or cumulative lifetime exposure. A cholestatic primary LT indication, acute rejection episodes, and fractures post-LT were not associated with BMD. Extracurricular physical activity, vitamin D, and calcium intake were not associated with BMD or fractures. Multivariate linear regression revealed increased time post-LT (P = 0.04) and higher BMI z score at time of DXA (P = 0.02) as the strongest independent variables associated with greater BMD. CONCLUSIONS: Neither corticosteroid exposure nor a cholestatic primary indication for LT influenced BMD, which was largely normal in this ambulatory group. Children and adolescents undergoing LT after the age of 10 years and those with low BMI post-LT may be at greatest risk of poor skeletal health later in life, and thus a potential target patient population to benefit from preventive interventions.

Cadmium is more toxic on volume bone mineral density than tissue bone mineral density.

It has been showed that Cd induces low areal bone mineral density, but we do not know the effect of Cd on cubic bone density. This study was aimed to investigate the effects of Cd on volumetric bone mineral density (VBMD) and tissue bone mineral density (TBMD) in male rats. Twenty-four Sprague-Dawley male rats were randomly divided into four groups that were given cadmium chloride by subcutaneous injection at doses of 0, 0.1, 0.5, and 1.5 mg/kg body weight for 8 weeks, respectively. Then, microcomputed tomography scanning was performed on the proximal tibia, and region of interest was reconstructed using microview software. The VBMD, bone volume fraction of rats treated with 1.5 mg Cd/kg, were significantly decreased compared to control (p < 0.01). The trabecular numbers of rats exposed to Cd were all significantly decreased relative to control (p < 0.05). The trabecular separation of rats treated with 1.5 mg Cd/kg was obviously increased compared to control (p < 0.01). However, Cd had no obvious influence on TBMD. Cd induced low VBMD but not TBMD; Cd effect on bone may be related with trabecular bone loss but not with trabecular bone demineralization.

Preproenkephalin (Penk) is expressed in differentiated osteoblasts, and its deletion in Hyp mice partially rescues their bone mineralization defect.

Although our understanding of the molecular mechanisms controlling osteoblast differentiation and function is steadily increasing, there are still many open questions, especially regarding the regulation of bone matrix mineralization. For instance, while there is hallmark evidence for the importance of the endopeptidase Phex, whose inactivation in Hyp mice or human patients causes X-linked hypophosphatemic rickets, it is still largely unknown how Phex controls bone mineralization since a physiological substrate for its endopeptidase activity has not been identified yet. Using a genome-wide expression analysis comparing primary calvarial osteoblasts, we have identified preproenkephalin (Penk) as a gene that is selectively expressed in mineralized cultures. Since a role of enkephalin in the regulation of bone remodeling has been suggested previously and since Leu-enkephalin is known to be cleaved by Phex, we analyzed whether Penk expression in osteoblasts is physiologically relevant. Through skeletal analysis of a Penk-deficient mouse model, we found that Penk expression is dispensable for bone development and remodeling since we could not detect any defect following nondecalcified bone histology and histomorphometry compared to wild-type littermates. When Penk was deleted in Phex-deficient Hyp mice, however, we observed a significant reduction of the osteoid enrichment at 24 weeks of age, whereas their disturbance of mineral homeostasis was not affected by the additional absence of the Penk gene. Taken together, our data provide the first in vivo analysis concerning the role of Penk in osteoblasts.

Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients.

Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency therefore would be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals, excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters, including osteoid indices, were quantified using the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels were measured for all patients. Statistical analysis was performed by Student's t test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15% of the analyzed patients presented with an osteoid surface per bone surface (OS/BS) of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in osteoid volume per bone volume (OV/BV) greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of bone volume per trabecular volume (BV/TV) throughout all ages and affected both sexes equally. While we could not establish a minimum 25(OH)D level that was inevitably associated with mineralization defects, we did not find pathologic accumulation of osteoid in any patient with circulating 25(OH)D above 75 nmol/L. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25(OH)D below 75 nmol/L and strongly argue that in conjunction with a sufficient calcium intake, the dose of vitamin D supplementation should ensure that circulating levels of 25(OH)D reach this minimum threshold (75 nmol/L or 30 ng/mL) to maintain skeletal health.

Homocysteine-lowering therapy or antioxidant therapy for bone loss in Parkinson's disease.

We investigated whether homocysteine (Hcy)- lowering therapy or an antioxidant prevented bone loss in Parkinson's disease (PD) patients taking levodopa. Forty-two PD patients with low bone mineral density (BMD) taking levodopa were randomly assigned to Hcy-lowering therapy (5 mg folate and 1500 microg vitamin B(12) daily), alpha-lipoic acid (alpha-LA) therapy (1200 mg daily), or control groups. Primary outcomes were BMD changes from baseline to 12 months. Secondary outcomes were changes in Hcy level, and C-telopeptide (CTX) levels at 12 months. Forty-one patients completed the study. Hcy-lowering therapy resulted in significantly greater BMD changes at the lumbar spine (4.4%), total femur (2.8%), and femur shaft (2.8%) than control (P = 0.005-0.023). BMD changes in the alpha-LA therapy group were similar to those of the control group, but changes at the trochanter (4.6%) were significantly greater in the alpha-LA therapy group than in the control group after adjustment for body mass index changes. Hcy concentrations decreased to 35.2% +/- 13.4% in the Hcy-lowering therapy group, but increased in other groups. Serum CTX levels at 12 months tended to be lower in the Hcy-lowering group (0.442 +/- 0.024 ng/mL) than control group (0.628 +/- 0.039 ng/mL) (P = 0.159). This small trial suggests that Hcy-lowering therapy may prevent bone loss in PD patients taking levodopa.

Bone degeneration and recovery after early and late bisphosphonate treatment of ovariectomized wistar rats assessed by in vivo micro-computed tomography.

Bisphosphonates are antiresorptive drugs commonly used to treat osteoporosis. It is not clear, however, what the influence of the time point of treatment is. Recently developed in vivo micro-computed tomographic (CT) scanners offer the possibility to study such effects on bone microstructure in rats. The aim of this study was to determine the influence of early and late zoledronic acid treatment on bone in ovariectomized rats, using in vivo micro-CT. Twenty-nine female Wistar rats were divided into the following groups: ovariectomy (OVX, n = 5), OVX and zoledronic acid (ZOL) at week 0 (n = 8), OVX and ZOL at week 8 (n = 7), and sham (n = 9). CT scans were made of the proximal tibia at weeks 0, 2, 4, 8, 12, and 16; and bone structural parameters were determined in the metaphysis. Two fluorescent labels were administered to calculate dynamic histomorphometric parameters. At week 16, all groups were significantly different from each other in bone volume fraction (BV/TV), connectivity density, and trabecular number (Tb.N), except for the early ZOL and control groups which were not significantly different for any structural parameter. After ZOL treatment at week 8, BV/TV, structure model index, Tb.N, and trabecular thickness significantly improved in the late ZOL group. The OVX and ZOL groups showed, respectively, higher and lower bone formation rates than the control group. Early ZOL treatment inhibited all bone microstructural changes seen after OVX. Late ZOL treatment significantly improved bone microstructure, although the structure did not recover to original levels. Early ZOL treatment resulted in a significantly better microstructure than late treatment. However, late treatment was still significantly better than no treatment.

Thyroid hormone-induced demineralisation of the vertebral skeleton of the eel, Anguilla anguilla.

The role of thyroid hormones (TH) in bone remodelling is controversial. Indeed, in humans, while they are necessary for normal growth and development, their overproduction can induce important mineral bone loss and osteoporosis. Intense bone resorption is a natural phenomenon also observed in some teleosts, during reproductive migration and fasting. Our work aimed at investigating the effects of chronic treatments with TH (thyroxin, T4 or triiodothyronine, T3) on bone resorption in a migratory fish, the European eel (Anguilla anguilla), a representative species of an ancient group of teleosts (Elopomorphs). The incineration method showed that TH induced a significant mineral loss in eel vertebral skeleton. Histology and histophysical (qualitative and quantitative microradiographs) methods were then applied to vertebral sections to determine which types of resorption were induced by TH. Quantitative image analysis of microradiographs showed that TH significantly increased the porosity of the vertebrae, demonstrating the induction of a severe bone loss. Histology revealed the appearance of large osteoclastic lacunae, indicating a stimulation of osteoclastic resorption. Quantitative image analysis of ultrathin microradiographs showed a significant increase of the size of osteocytic lacunae, indicating a stimulation of periosteocytic osteolysis. Finally, quantitative microradiographs indicated a significant fall of mineralisation degree. TH treatments did not stimulate the production of the calcium-bonded lipo-phospho-protein vitellogenin, indicating that TH-induced bone demineralisation was not mediated by any indirect effect on vitellogenesis. Our study demonstrates that TH may participate in the mobilisation of bone mineral stores in the eel, by inducing different types of vertebral bone resorption, such as osteoclastic resorption and periosteocytic osteolysis. These data suggest that the stimulatory action of TH on bone resorption may be an ancient regulatory mechanism in vertebrates.

Computerized quantification of joint space narrowing and periarticular demineralization in patients with rheumatoid arthritis based on digital x-ray radiogrammetry.

OBJECTIVES: The aim of our work was to evaluate digital x-ray radiogrammetry (DXR) for the quantification of disease-related periarticular demineralization and computerized analysis of joint space distances (JSDA) for the measurement of joint space narrowing as a new diagnostic method for the early detection of joint-associated alterations and for monitoring disease progression in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Digital radiographs in 313 patients with varying severity of RA were performed annually and assessed by 2 radiologists using modified Larsen and also the Sharp scores within an observation period of 3 years. The hand radiographs underwent measurements of bone mineral density (BMD) and metacarpal index (MCI) by DXR, as well as computerized JSDA at the metacarpal-phalangeal articulation (JSD-MCP) for a cross-sectional and longitudinal study design. RESULTS: Both DXR-BMD (-29.6%; P < 0.01) and DXR-MCI (-31.0%; P < 0.01) revealed a notable reduction dependent on the severity of RA (from grade 1 to grade 5 of the modified Larsen score); the severity dependent decrease of mean JSD-MCP ranged from -31.9% (P < 0.01; Sharp erosion part) to -39.1% (P < 0.01) for the modified Larsen score. Over an observation period of 3 years, a significant decrease of DXR-BMD (-22.3%) and DXR-MCI (-23.3%) as well as JSD-MCP mean (-17.5%) was observed (P < 0.05), whereas an accentuated decline of DXR and JSDA parameters was verified for patients without disease-modifying antirheumatic drugs or methotrexate therapy. CONCLUSION: Computerized analysis of hand radiographs by DXR and JSDA is a promising approach to assess the severity and to monitor the progression of RA because DXR and JSDA are timely able to measure periarticular demineralization and also narrowing of JSD-MCP dependent on the severity, the medical treatment and the course of RA.

[The preliminary study on the characteristics of mandible and condyle in dentin matrix protein-1 gene knockout mice].

OBJECTIVE: To study the characteristics of mandible and condyle in Dmp1 gene knockout mice, and to investigate the role of Dmp1 in the osteogenesis and mineralization of bone and cartilage. METHODS: Dmp1-/-mice were executed at birth, 2 weeks, 2 months, 3 months and 5 months, and the mandible was taken out for physical, radiography, transmission electron microscopic, and histological examination. The difference between Dmp1 knockout mouse (ko) and wild type mouse (wt) in bone development, bone densitometry and histology were compared. RESULTS: There were obvious changes in the mandible and condyle of Dmp1-/-mouse, such as incomplete ossification, low density, decreased volume and condyle cartilage degeneration. CONCLUSIONS: Dmp1 is the key factor in the formation of growth plates and secondary ossification center, and plays an important role in the process of bone and cartilage formation and bone nodule remodeling. Dmp1 may be the candidate gene that controls the development of mandible and cartilage.

Muscle strength is a determinant of bone mineral content in the hemiparetic upper extremity: implications for stroke rehabilitation.

Individuals with stroke have a high incidence of bone fractures and approximately 30% of these fractures occur in the upper extremity. The high risk of falls and the decline in bone and muscle health make the chronic stroke population particularly prone to upper extremity fractures. This was the first study to investigate the bone mineral content (BMC), bone mineral density (BMD), and soft tissue composition of the upper extremities and their relationship to stroke-related impairments in ambulatory individuals with chronic stroke (onset >1 year). Dual-energy X-ray absorptiometry (DXA) was used to acquire total body scans on 56 (22 women) community-dwelling individuals (>or=50 years of age) with chronic stroke. BMC (g) and BMD (g/cm2), lean mass (g), and fat mass (g) for each arm were derived from the total body scans. The paretic upper extremity was evaluated for muscle strength (hand-held dynamometry), impairment of motor function (Fugl-Meyer motor assessment), spasticity (Modified Ashworth Scale), and amount of use of the paretic arm in daily activities (Motor Activity Log). Results showed that the paretic arm had significantly lower BMC (13.8%, P<0.001), BMD (4.5%, P<0.001), and lean mass (9.0%, P<0.001) but higher fat mass (6.3%, P=0.028) than the non-paretic arm. Multiple regression analysis showed that lean mass in the paretic arm, height, and muscle strength were significant predictors (R2=0.810, P<0.001) of the paretic arm BMC. Height, muscle strength, and gender were significant predictors (R2=0.822, P<0.001) of lean mass in the paretic arm. These results highlight the potential of muscle strengthening to promote bone health of the paretic arm in individuals with chronic stroke.

Bone loss in the contralateral asymptomatic hand in patients with complex regional pain syndrome type 1.

Regional osteoporosis was seen radiographically in clinically affected areas in patients with complex regional pain syndrome type 1 (CRPS1). The aim of the this study was to investigate whether bone loss developed in the contralateral hand in patients with unilateral CRPS1 of the hand. Thirty-two patients with CRPS1 of the hand were included in this study. Bone mineral density was measured in the left proximal femur and both ultradistal radiuses, using dual-energy X-ray absorptiometry. The subjects were classified as grades 1 to 3 according to the T-score of both ultradistal radiuses (densitometric grades): grade 1, both radiuses were normal; grade 2, bone loss was determined only in the affected radius; and grade 3, there was bone loss in both radiuses. Twenty (62.5%) patients had bone loss in the affected hand; 11 patients (34.4%) had bone loss only on the affected side and 9 patients (28.1%) had bone loss on both sides. The mean duration of the period between the diagnosis of the injury and the measurement of bone density was 1.9 +/- 0.6 months in patients with grade 1, 3.1 +/- 1.0 months in patients with grade 2, and 5.5 +/- 2.2 months in patients with grade 3. The Spearman test showed a significant correlation between the period of injury and the densitometric grade ( R = 0.774; P = 0.0001). In conclusion, the current study of patients with CRPS1, showed that the bone loss in the asymptomatic contralateral hand developed at a later stage than that in the affected hand. This bone loss was less frequent and of a lower degree in the asymptomatic contralateral hand than in the affected hand. The bone loss in the asymptomatic contralateral hand could be explained by the loss of sympathetic tone in CRPS1 and contralateral sympathetic innervation.

Protracted systemic changes in bone biology after segmented unloading in the rat.

To investigate whether the decreased bone formation observed in most experimental situations of disuse was caused by an increased inhibition by the bone microenvironment of osteoblast (OB) proliferation, we studied the inhibiting power on ROS 17/2.8 proliferation of the bone marrow extracellular fluid (IPEF) in loaded and unloaded bones of rats submitted to two situations of partial disuse: tail suspension (TS) for 3 days to 2 weeks and around the knee tenectomy (KT) for 2-10 weeks. Histomorphometric parameters and osteoblast precursors dynamics were studied in parallel. Bone volume was lost in the unloaded bones, but not in loaded bones, in both experimental situations. Bone formation was low at early times (7-14 days) in TS rats. However, in KT at later times (4-10 weeks), the osteoblastic index of the unloaded tibia was increased. IPEF was not increased in the unloaded bones 3-7 days after TS. It was decreased later in the course of unloading (after 2 weeks of TS and 2-10 weeks after KT). This decrease was observed in the loaded bones as well. Unexpectedly, we also found that the number of FCFUs was decreased in both loaded and unloaded limbs in TS and KT, and that the yield of cells obtained in primary culture from tibial metaphysis was decreased in both tibiae from KT animals. These data show that an increased IPEF does not play a role in the early inhibition of bone formation responsible for the loss of bone after unloading in the TS model. Its later decrease could be permissive for the increased osteoblastic index observed in the KT model. They also show that, contrary to the usual assumptions, bone biology is changed all over the skeleton after partial unloading, even if the changes result in bone loss in the unloaded bones only. Thus, as yet, unidentified systemic factors probably superimpose on the local factors that control bone volume.

Late-onset spondyloarthropathy mimicking reflex sympathetic dystrophy syndrome.

Atypical presentations are common when spondyloarthropathy develops in older patients. We report two cases initially mistaken for reflex sympathetic dystrophy syndrome (RSDS). Both the patients were men, aged 62 and 75 years, respectively, with marked painful edema of a foot. One patient reported a moderate-energy trauma as the triggering event. Severe diffuse demineralization was noted on radiographs and diffuse hyperactivity on bone scans starting at the early vascular phase. These findings suggestive of RSDS led to treatment with calcitonin, griseofulvin, and pamidronate, all of which were ineffective. Laboratory tests showed severe inflammation, promoting investigations for other conditions. Spondyloarthropathy was diagnosed based on oligoarthritis with sacroiliitis, presence of HLA B27, and a favorable response to non-steroidal antiinflammatory therapy. In older patients, edema of the foot with severe demineralization and the laboratory evidence of inflammation should suggest a spondyloarthropathy.