What is your diagnosis? Metaphyseal osteopathy.
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Osteoporosis is the most frequent demineralizing disease. However, when a demineralized vertebra is identified, other diseases must be ruled out in the course of diagnosis. Through three clinical cases, we analyze pitfalls that have delayed the diagnosis of one rare, but unfortunately lethal, aetiology: multiple myeloma.
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We demonstrated that administration of a bisphosphonate, YH529, prevents the development of disuse atrophy of the hind limbs induced by tail-suspension in rats. Since tail suspension is accompanied by an increase in the secretion of stress hormones, we studied whether administration of bisphosphonate affects the secretion of stress hormones during that procedure. Tail suspension was carried out in a metabolic cage by connecting a wire inserted through tail bone to the ceiling of the cage. The control rat received the same treatment but was not suspended. YH529 or a vehicle (PBS=phosphate buffered saline) was administered daily starting 3 days before the commencement of tail suspension. Urine samples were collected before the wire was inserted (day 0), on the day of insertion (day 1) and 3, 5 and 7 days after. In the control rats receiving PBS, urinary excretion of corticosterone and epinephrine did not change throughout the 7-day experimental period. In the control rats receiving YH529, urinary excretion of corticosterone increased significantly on the day of tail-piercing and wiring but then returned to the prior level. This increase was not observed in the control group receiving PBS. In the tail suspended rats, excretion of corticosterone and epinephrine increased significantly in both PBS and YH529 groups, the highest level being observed on the first day of tail suspension. Although statistically not significant, corticosterone excretion on day 1 of tail suspension was higher in the YH529 groups than that in the PBS group. It is thus suggested that administration of YH529 causes an augmented response to stress load.
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To elucidate the mechanism involved in the development of disuse atrophy of bone by skeletal unloading, changes in osteocalcin and alkaline phosphatase mRNAs, markers for bone formation, were studied in the hind limb bones of tail-suspended rats. Tail suspension for 8 and 14 days resulted in a significant decrease in osteocalcin mRNA in the femur when compared with age-matched non-suspended controls. Serum 1,25-dihydroxyvitamin D3 decreased to 60% of the control level after 8 days of skeletal unloading but regained almost normal levels over the next 7 days. Since it is known that vitamin D3 up regulates and glucocorticoid down regulates transcription of the osteocalcin gene, the endocrine response evoked by tail suspension may have aggravated the disuse atrophy caused by skeletal unloading in this study.
Anti Orthostatic Hypokinetic posture in rats by tail suspension for 15 days (d) simulates the deconditioning effects of weightlessness on the weight bearing bones. The present study evaluates the effects of daily 4 hour (h) weight support (WS) during simulated weightlessness (S-W) in preventing these changes. Adult male albino rats were divided into three groups as (i) Control (CON, n = 12), (ii) Hind limb unweighing by tail suspension for 15 d (HU, n = 18), (iii) HU with daily 4 h WS (4 HRWS, n = 11). After 15 d tibia from all the animals were removed and subsequently dried, ashed and then calcium content of the bones were determined. HU showed reductions in the water content by 35.8%, organic matrix by 12.2% and calcium content by 33.4% of tibia. 4 h WS during S-W resulted in complete prevention of water loss and organic matrix loss and partial prevention of the loss of calcium content. Calcium content of tibia in 4 HRWS remained 15.2% less as compared to CON. These findings indicate that 4 h WS is partially successful in preventing the demineralisation effects of S-W on weight bearing bone tibia.
As a direct consequence of exposure to microgravity astronauts experience a number of physiological changes, which can have serious medical implications when they return to Earth. Most immediate and significant are the head-ward shift of body fluids and the removal of gravitational loading from bone and muscles, which lead to progressive changes in the cardiovascular and musculoskeletal systems. Cardiovascular adaptations result in an increased incidence of orthostatic intolerance (fainting) post-flight, decreased cardiac output and reduced exercise capacity. Changes in the musculoskeletal system contribute significantly to the impaired functions experienced in the post-flight period. The underlying factor producing these changes is the absence of gravity. Countermeasures, therefore, are designed primarily to simulate Earth-like movements, stresses and system interactions. Exercise is one approach that has received wide operational use and acceptance in both the US and Russian space programmes, and has enabled humans to stay relatively healthy in space for well over a year. Although it remains the most effective countermeasure currently available, significant physiological degradation still occurs. The development of other countermeasures will therefore be necessary for longer duration missions, such as the human exploration of Mars.
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To assess the potential value of intermittent artificial gravity as an efficient countermeasure, our previous studies have showed that daily 4-h standing (STD) is sufficient in counteracting muscle atrophy but not bone atrophy induced by simulated microgravity. The aim of the present study was to determine whether intermittent gravitational loading by daily 2-h or 4-h, +45 degrees head-up tilt (HUT) is more effective than STD in counteracting muscle and, particularly, bone atrophy due to simulated microgravity. Sprague-Dawley male rats weighing 290-300 g were subjected to a 28-d tail-suspension to simulate microgravity deconditioning. Daily HUT for 2, or 4 h was used to provide intermittent gravitational loading in foot-ward and tail-ward directions. The results showed that 4 h/d HUT was sufficient, and 2 h/d was less effective, in preventing adverse changes in muscle weights, fiber types, and cross-sectional areas (CSA) of muscles due to a 28-d simulated microgravity. The % protections by 4 h/d HUT in maintaining the CSAs of type I fibers in soleus, medial and lateral gastrocnemius and extensor digitorum longus muscles were 103%, 82%, 102%, and 83%, respectively. However, according to changes in physical and mechanical properties of femur, daily 4-h HUT was ineffective in attenuating the adverse changes in bone due to a 28-d simulated microgravity. Reductions in wet, dry, and ash weights and decreases in mechanical strength of femur did not show significant improvement by daily 2-h or 4-h HUT. Taken together, the findings indicate that the countermeasure effectiveness of daily 2-h or 4-h HUT for muscles is comparable with that by daily STD with the same durations. Daily 4-h HUT, as 4-h STD, is also ineffective in attenuating adverse changes in bone mass, but seems partially effective in preventing declines in mechanical properties due to simulated microgravity.
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.
We have reported that centrifuge-induced artificial gravity with ergometric exercise could reduce developing cardiovascular deconditioning in humans. In the present study, we examined this load could prevent the myatrophy and osteoporosis induced by head-down bedrest for 20 days. Subjects were ten healthy male volunteers with informed consent. They were requested to lie down at -6 degrees for 20 days, and evaluation for cardiovascular deconditioning, myatrophy, and osteoporosis. As the result, high G-load with low intensity exercise suppressed the orthostatic intolerance and increase in serum osteoporotic marker, whereas low G-load with high intensity ergometric exercise maintained the maximal oxygen intake, heart dimension, and prevented myatrophy. The combination of high/low G-load with low/high intensity exercise will determine the optimal protocol for prevention of cardiovascular deconditioning, myatrophy, and osteoporosis.
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This study determined the early natural history of disuse osteoporosis in the ulna and radius. Six women and 2 men (mean age, 48.5 years; range, 35-60 years) having surgery on their wrists or hands had bone mineral density determined by single energy xray absorptiometry at 4 sites of the distal radius and ulna before operation, at cast removal (mean, 4.9 weeks after surgery), and after an average of 4.7 weeks of remobilization and hand therapy. A control group of 4 men and 4 women (mean age, 35.6 years; range, 24-46 years) had bone mineral density measurements of both forearms taken initially and again 5 weeks later. The patients had significant loss in bone mineral density at the ulna and distal sites of the forearm after 4.9 weeks of immobilization. Loss of bone mineral density continued at all 4 sites even after 4.7 weeks of remobilization and hand therapy. Bone mineral density increased significantly at the ultradistal radius of the contralateral forearm (which was not operated on) after 4.9 weeks, but this gain was no longer significant after 4.7 weeks of remobilization of the surgically treated forearm, suggesting that increased activity of the nonimmobilized forearm increased bone mineral density at certain sites. No changes in bone mineral density were seen in the control group. Immobilization of the forearm after hand or wrist surgery significantly decreases bone mass in the distal radius and ulna.
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Athletic amenorrhea is seen frequently in competitive athletes and is strongly associated with diminished bone mineral density and disordered eating behavior. It is important, however, to note that most of the studies performed to date have been influenced significantly by selection bias. A recent Scandinavian study has shown that the great majority of women who exercise at regular and moderate levels are not at significant risk for athletic amenorrhea and its adverse effect on bone mineral density. Nevertheless, athletic amenorrhea should never be minimized when detected, and appropriate evaluation should be undertaken to prevent the adverse effects of prolonged amenorrhea on skeletal integrity.
In investigations of the process of bone destruction caused by chronic otitis media complicated with cholesteatoma, we proposed previously a hypothesis to explain its mechanism. In the present study, we substitute a synthetic auditory ossicle (Apaceram) for the bone to simplify the model system of experiments for our hypothesis. Its process was studied on a model simulation in vitro, in vivo and clinically at molecular level, using laser-Raman spectrometry. An increase of conductivity in both the saline solution and double-distilled water immersed Apaceram indicated demineralization depending on time lapse. The process of demineralization was revealed by the Raman spectral profiles as shown by narrowing a half-peak breadth (p < 0.01) of v1 signal (PO4(3-), 960 cm-1) and the disappearance of the shoulder at circa 950 cm-1 on the Apaceram surface implanted for 6 months. On the other hand, the process of remineralization was revealed in vivo by the spectral profiles: 1) a broader half-peak breadth (p < 0.01) of v1 signal on the Apaceram surface implanted for 10 months than that implanted for 6 months; 2) a weak reappearance of the shoulder at ca. 950 cm-1 on the Apaceram surface after 10 months; 3) four signals (v1 through v4) of PO4(3-) on the HOAP observed for inside the Apaceram shaft and 4) a weak v1 signal on both the granular fluorescent substance in the clinical case and the high density area of subcutaneous tissue after contact with the Apaceram in rats for 3 months. Judging from these investigations, it is proposed that the mechanism of bone destruction associated with cholesteatoma is a form of de- and remineralization.