Estrogen and cancellous bone loss in the fowl

Long-term follow-up study with positron emission tomography (PET) has been conducted in a patient with superficial siderosis for ten years. A 63-year-old right-handed woman began to exhibit a cerebellar ataxia when she was 52 years old. Thereafter she has been exhibiting a slowly progressive course of pyramidal signs, hearing loss, anosmia, bilateral sciatica and memory disturbance in addition to the cerebellar ataxia. Series of x-ray CT and MRI disclosed a progressive atrophy of the cerebellum, specifically in the superior vermis, and a mild diffuse atrophy in the cerebral hemispheres, whereas no significant atrophy was seen in the brainstem. A marked hypointensity was seen along the rim of the brain structures including brainstem, cerebellum, sylvian fissures and the medial temporal lobes on MR T 2-weighted images. This hypointensity was also found at the edges of the third and fourth ventricles. These findings were regarded as haemosiderin deposit. By using oxygen-15, PET was carried out repeatedly with ten-year interval. In the initial PET study, both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were mildly decreased in the cerebellar hemispheres and the occipital cortices. The follow-up PET study revealed a progressive reduction of CMRO2 in the brainstem, cerebellar hemispheres and temporal cortices including the hippocampus in which the haemosiderin deposition was marked on MRI, whereas the reduction of CBF was not advanced as compared with CMRO2. It was suggested that the progressive reduction of CMRO2 in the brain sites where the haemosiderin deposition was observed on MRI reflected the clinical course of neurological deterioration.     

What determines peak bone mass and bone loss?

Bone mass at any point in life represents a balance between the amount of bone laid down during growth and development and the amount of bone lost with ageing. At a cellular level, these changes in bone mass occur as the result of bone remodelling; a process whereby bone resorbing cells (osteoclasts) and bone forming cells (osteoblasts) remove and replace small packets of bone at discrete points throughout the skeleton. This process is in turn regulated by a complex interaction between genetic factors and environmental influences such as nutrition and exercise, which affect bone cell function both directly and indirectly by altering the production of local and systemic hormones that modulate bone cell activity. In this chapter, I shall review the relative importance of genetic and environmental factors in regulating bone growth, peak bone mass, and bone loss. Discussion of the genetic aspects shall focus on recent data linking polymorphisms in candidate genes to bone mass and bone loss, and on the possible role which gene-environment interactions may have in regulating these processes.     

Ectopic hematopoietic bone marrow in the appendicular skeleton after trauma

METHODS: Combined bone scanning and immunoscintigraphy (IS) with 99mTc-monoclonal antigranulocyte antibodies were performed in two patients with suspected reactivation of chronic osteomyelitis of the lower extremity. Because bone scanning and IS were strongly positive, both patients underwent surgical intervention. RESULTS: Macroscopic findings did not show purulent infection and microbiologic results remained negative, but histology revealed unexpected ectopic bone marrow, explaining the strong uptake on IS. One patient exhibited active hematopoietic bone marrow at the former fracture site of the tibial bone. The second patient presented with interspersed bone marrow in the cortical bone of the femoral diaphysis after several intramedullary surgical procedures. CONCLUSION: Unexpected ectopic hematopoietic marrow may occur in the appendicular skeleton after trauma and repeated surgical interventions. The bone marrow shows a physiologic uptake with IS and may be misinterpreted as granulocyte accumulation due to infection. This may lead to false-positive diagnosis in cases of suspected osteomyelitis.     

Alveolar bone loss and restorative dentistry in the primary molars

Stab wounds to the abdomen can present a diagnostic dilemma to the trauma surgeon, especially in the thoracoabdominal region. Patients with lower chest and upper abdominal stab wounds are at risk for both intraabdominal and cardiac injury. Current options in the evaluation of these patients include mandatory laparotomy, diagnostic peritoneal lavage, thoracoscopy, sonography, and observation. Each has its own inherent advantages and disadvantages, but none of them represents the gold standard. Herein is reported a case of a patient with an epigastric stab wound who underwent diagnostic laparoscopy and laparoscopic transdiaphragmatic pericardial window to rule out both peritoneal penetration and cardiac injury.     

Apoptosis and therapy of malignant diseases of the hematopoietic system

Apoptosis is essential in the pathogenesis of hematological diseases. A tumor develops, if the balance between cell division and cell death is disturbed. In recent years many genes involved either in blocking or inducing this process have been identified. Additionally, several cytokines which influence apoptosis have been found. Some of these cytokines could also play a role in the development of resistance to chemotherapeutic agents. Many anticancer drugs exert their action via apoptosis. A strategy to selectively induce apoptosis of tumor cells without altering healthy cells and thus reducing the side effects of therapeutic regimens is a major goal for future development of new therapeutic techniques. Blocking the factors which are responsible for resistance is another promising therapeutic approach and could further improve the clinical outcome and finally prolong the life of patients.     

Magnesium deficiency and bone loss after cardiac transplantation

Magnesium depletion adversely affects many phases of skeletal metabolism and has been implicated as a risk factor in several forms of osteoporosis. Magnesium deficiency has also been reported after cardiac transplantation. To evaluate whether altered magnesium homeostasis could be related to the pathogenesis of early bone loss after cardiac transplantation, we prospectively measured serum and urinary magnesium and evaluated them with respect to biochemical indices of mineral metabolism and rates of bone loss. The study population included 60 patients (45 men, 15 women) aged 53 +/- 11 years (SD) with measurements of biochemistries and bone mineral density by dual-energy X-ray absorptiometry before and 3 months after transplantation. All received prednisone, cyclosporine A, and azathioprine, plus calcium (1000 mg) and vitamin D (400 IU). After transplantation, serum magnesium decreased by 16 +/- 15% (SD) from 2. 0 +/- 0.3 mg/dl to 1.6 +/- 0.2 mg/dl (normal 1.8-2.2 mg/dl; p < 0. 0001), accompanied by an increase in the fractional excretion of magnesium (7.1 +/- 3.9% to 13.3 +/- 5.6%; p < 0.0017). Forty-three patients with low 3-month serum magnesium levels (相似文献   

Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats

Interleukin-1 (IL-1), a cytokine produced by bone marrow cells and bone cells, has been implicated in the pathogenesis of postmenopausal osteoporosis because of its potent stimulatory effects on bone resorption in vitro and in vivo. To investigate whether IL-1 plays a direct causal role in post ovariectomy bone loss, 6-mo-old ovariectomized rats were treated with subcutaneous infusions of IL-1 receptor antagonist (IL-1ra), a specific competitor of IL-1, for 4 wk, beginning either at the time of surgery or 4 wk after ovariectomy. The bone density of the distal femur was measured non invasively by dual-energy X-ray absorptiometry. Bone turnover was assessed by bone histomorphometry and by measuring serum osteocalcin, a marker of bone formation, and the urinary excretion of pyridinoline cross-links, a marker of bone resorption. Ovariectomy caused a rapid increase in bone turnover and a marked decrease in bone density which were blocked by treatment with 17 beta estradiol. Ovariectomy also increased the production of IL-1 from cultured bone marrow cells. Ovariectomy induced-bone loss was significantly decreased by IL-1ra treatment started at the time of ovariectomy and completely blocked by IL-1ra treatment begun 4 wk after ovariectomy. In both studies IL-1ra also decreased bone resorption in a manner similar to estrogen, while it had no effect on bone formation. In contrast, treatment with IL-1ra had no effect on the bone density and the bone turnover of sham-operated rats, indicating that IL-1ra specifically blocked estrogen-dependent bone loss. In conclusion, these data indicate that IL-1, or mediators induced by IL-1, play an important causal role in the mechanism by which ovariectomy induces bone loss in rats, especially following the immediate post ovariectomy period.     

The effects of smoking on bone mass and the rates of bone loss among elderly Japanese-American men

Bone density and bone loss rates were examined among Japanese-American men categorized as current cigarette smokers, past smokers, and nonsmokers. The design included a retrospective study of smoking and bone density and a prospective study of current smoking and bone loss rates. The mean length of follow-up was 5 years; the setting was the island of Oahu. The subjects included 1303 men in the Hawaii Osteoporosis Study, 51-82 years old at their initial examination. Twenty percent were current smokers, 45% past smokers, and 35% had never smoked. Their bone density was measured at the distal and proximal radius and calcaneus using single photon absorptiometry. Compared with never smokers, current and past smokers had significantly lower bone density, especially in the predominantly cancellous calcaneus (4.8 and 4.3% lower, respectively) and partially trabecular distal radius (1.8 and 3.3% lower, respectively). The magnitude of the smoking effect was linked strongly to the duration of smoking and also to the number of cigarettes smoked. Bone loss rates subsequent to the initial measurement were greater in the current smokers than the never smokers (20.5, 27.2, and 9.7% greater at the calcaneus, distal, and proximal radius, respectively) but the differences did not achieve significance. Smokers of more than one pack per day had 32.0, 77.6, and 30.7% greater loss rates than never smokers in these same sites; the difference achieved significance at the distal radius. The results from the distal radius suggest that these smokers may increase their fracture risk 10-30% per decade of smoking. The adverse effects of smoking appeared to be greater in cancellous than cortical bone.     

Effect of menopause on femoral and vertebral bone loss

The aim of this study was to investigate the effect of menopause on bone loss in the proximal femur and the lumbar spine. The rates of change in bone mineral density (BMD) were measured longitudinally by dual X-ray absorptiometry (DXA) at the femoral neck (FN), Ward's triangle (WT), and trochanter (TR) together with the lumbar spine in 81 healthy postmenopausal women (45-65 years of age) who had passed a natural menopause, 6 months to 12 years before. A significant correlation between the rate of change and interval since menopause was evidenced. The best fit of the data was a binomial function of interval since menopause at the spine, FN, and WT and a simple linear regression at TR level. At each skeletal site, the rate of bone loss (mean +/- SD) was significantly different (p<0.05) and twice as high in women who were between 6 months and 2 years postmenopausal at enrollment (FN, -1.82 +/- 1.1%; WT, -2.43 +/- 1.7%; TR, -1.12 +/- 1.7%) than in those who were beyond 5 years of menopause (FN, -0.48 +/- 0.8%; WT, -0.68 +/- 2.1% TR, 0.41 +/- 1.2%). A poor correlation (r = 0.39 - 0.42, p<0.001) was found between the rate of vertebral and that of femoral postmenopausal bone loss. This study demonstrates that menopause is associated with a rapid and transient bone loss in BMD of the proximal femur, which declines with time after 3 years. These data suggest that therapy should be initiated as early as possible after menopause to prevent bone loss.     

Prevention of post-oophorectomy bone loss with Tibolone

The organic symptoms and results of coagulation tests of disseminated intravascular coagulopathy (DIC) in 17 patients with infection were compared with those in 12 patients with malignancy. The infectious diseases were mainly sepsis and pneumonia, and the malignancy was mainly lung cancer. The mean antithrombin III (AT III) before treatment was 54% in infection and 68% in malignancy, and the AT III values improved after administration of 1500 U of AT III concentrates per day. The mean thrombin-antithrombin complex level decreased from 22 ng/ml to 9 ng/ml after the treatment in infection, but it increased in malignancy. There were no differences in DIC scores between infection and malignancy before treatment; however, the scores were significantly more improved in infection than in malignancy after treatment (p < 0.05). The fibrin/fibrinogen degradation product level, platelet count, and fibronectin level were also significantly more improved in infection than in malignancy. This better response to treatment in infection than in malignancy is probably due to eradication of the causative organisms by antibiotics in infection. These data suggest that therapy against both DIC and the underlying disease is crucial for successful treatment.     

Intermittent cyclical etidronate in the prevention of corticosteroid-induced bone loss

We describe here a unique case of congenital adrenal hyperplasia (CAH) accompanied by Klinefelter syndrome. A Japanese boy was diagnosed as having CAH caused by 21-hydroxylase deficiency at birth, but was untreated thereafter until age 10. In the meantime he showed marked acceleration in somatic growth with sexual precocity by age 9, at which time growth completely stopped. During regular follow-ups at our clinic and steroid treatment after age 10, he was recognized as having bilateral small and firm testes. A chromosomal examination and a testicular biopsy revealed a complication of 47, XXY Klinefelter syndrome with CAH. Association of these two diseases has not been reported so far, and the present case is the first one to our knowledge.     

Free transfer of the vascularized fibula in pseudarthrosis and femoral bone loss

The authors report their experience of femoral reconstruction by free fibular graft transfer. Twenty eight patients were operated on between 1977 and 1988. The average follow-up was 7 years and 3 months. The etiology of most of the cases was a post traumatic lesion (70 per cent). Loss of substance was found in 19 cases. 60 per cent of these were septic. The approach was usually posterior and vessels from the sciatic nerve were used. Union was obtained in 89 per cent of the cases. In 65 per cent of the cases union occurred in less than 1 year. In 1 out of 4 cases graft thickening was necessary and achieved by secondary bone grafts. The comparison of this technique with standard treatments evidenced a definite superiority of vascularized bone grafts in cases of septic pseudarthrosis and significant losses of bone.     

Calculus deposits and bone loss on the teeth of Romano-British and eighteenth-century Londoners

The relation between dental calculus and periodontal disease is not clear but it is generally recognized that calculus is a significant pathogenetic factor. Skeletal material has previously been used to study some aspects of chronic adult periodontitis but few studies have quantified the extent of calculus in ancient populations and its relation to changes in alveolar bone height. This study records the presence and extent of calculus and its relation to alveolar bone loss in a Romano-British and eighteenth-century London population. There were significant differences in calculus deposition in the two populations but this appeared to have little effect on changes in alveolar bone contour. It is suggested that the amount of calculus may be related to diet but that changes in alveolar bone height seem to be independently controlled.     

Complicated gastrointestinal bleeding of neoplastic diseases of the hematopoietic system

The incidence of gastrointestinal bleeding has been reported as 10-30% of the patients with neoplastic diseases of the hematopoietic organ. The pathogenesis of gastrointestinal bleeding is multifactorial; direct leukemic cell infiltrations mucosal changes ensuing from bone marrow suppression or immunodeficiency states, infections due to various organisms, and preceding peptic ulcers. Once the diagnosis of hematopoietic neoplasm has been established, complete gastrointestinal work-up by endoscopy, CT-scanning or MRI should be mandatory. Early examination of the gastrointestinal tract has advantages of recognition of preceding peptic ulcers and their treatment, as well as providing prophylactic steps to the gastrointestinal mucosa vulnerable to hemorrhage. The prognosis of gastrointestinal bleeding complicated with hematopoietic malignancies seems to be poor due to the fact that DIC, multiorgan failures or fatal infections are seriously involved in their terminal stages.     

The cellular basis of bone turnover and bone loss: a rebuttal of the osteocytic resorption--bone flow theory

There is now sufficient evidence to conclude that the osteocytic resorption--bone flow theory of bone turnove is untenable. According to this theory bone is resorbed not from the surface by osteoclasts but from within by osteocytes, towards which bone flows through tissue space away from bone forming surfaces. The need to invoke resorption by osteocytes stems from the belief that too few osteoclasts are present to account for normal bone resoption, a belief which reflects unawareness of the enormous capacity of the osteoclast and the rapidity of its advance. The belief that osteocytes resorb substantial amounts of bone rests on invalid conclusions from indirect techniques, various artifacts of specimen processing and unawareness of the microscopic characteristics of woven bone. Osteocytes enlarge their lacunae by resorbing bone only as a prelude to resorption from the surface, the osteocyte and osteoclast working together as a resorbing unit. The belief that bone can flow is incompatible both with the physical properties of bone and with a substantial body of evidence relating to Haversian remodelling; the experimental data purporting to demonstrate such flow can all be explained by conventional concepts of bone turnover.     

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

OBJECTIVE: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. DESIGN: Secondary analysis of a 10-year follow-up study (1979 1989) among postmenopausal women in the Netherlands. SUBJECTS: From the original population of 154 women, 32 women were selected with an annual rate of radial bone loss of < or = 0.5% over the first 5 years of the study and 35 women with a rate of > or = 2.5% per year. METHODS: The isoflavonoids genistein, daidzein and equol, and the lignan enterolactone were determined by gas chromatography mass spectrometry in aggregate samples from annually collected urine samples. Cortical bone density of the radius had previously been measured annually by single-photon absorptiometry. RESULTS: Excretion of isoflavonoids did not differ between both groups, although in multivariate analysis equol excretion was weakly positively associated with rate of bone loss in the 5 years after the menopause. Enterolactone excretion was significantly higher in the group with high rate of bone loss. This positive association remained in multivariate linear regression analysis after adjustment for age, years since menopause, body mass index and intake of calcium, vegetable protein and dietary fibre. CONCLUSIONS: Enterolactone excretion is likely to be an indicator of consumption of grains and legumes; it is not clear whether the observed positive association with rate of bone loss is a causal one. Our results do not support a preventive effect of low, unsupplemented dietary intake of phyto-oestrogens on postmenopausal cortical bone loss. However, no conclusions can be drawn about effects of higher doses of phyto-oestrogens.