Aseptic necrosis of unilateral scaphoid bone in systemic lupus erythematosus.

An SLE patient developed aseptic necrosis of the right scaphoid bone 4 years after an episode of aseptic necrosis of bilateral femoral heads caused by corticosteroid treatment. Since the aseptic necrosis of the right scaphoid bone was preceded by the insidious exacerbation of SLE as evidenced by facial erythema, it was considered to be a result of vasculopathy due to active SLE. It took 14 months to make a correct diagnosis of the aseptic necrosis of the scaphoid bone by a chanced roentgenogram for the routine evaluation for osteoporosis. Therefore, the importance of an awareness of this possibility and repeated radiographic examinations is emphasized for the correct diagnosis of joint manifestations in SLE.     

Role of estrogen on bone in the human male: insights from the natural models of congenital estrogen deficiency

The reports of congenital estrogen deficiency - notably, estrogen resistance and aromatase deficiency - have completely changed our knowledge on the role of estrogen on bone in males. Particularly, the bone changes at puberty, which were classically considered androgen-dependent, are now considered to be induced at least in part by estrogen action. Clinical cases of congenital estrogen deficiency have clearly demonstrated that the role of estrogens in epiphyseal closure, skeletal proportions and bone mineralization is crucial not only in women but also in men. In addition progress have been made in the treatment of such a rare disease even though further studies are needed to a definitive understanding of this issue.     

Estrogens are essential for male pubertal periosteal bone expansion

The skeletal response to estrogen therapy was studied in a 17-yr-old boy with congenital aromatase deficiency. As expected, estrogen therapy (1 mg estradiol valeriate/d from age 17 until 20 yr) normalized total and free testosterone and reduced the rate of bone remodeling. Dual-energy x-ray absorptiometry-assessed areal bone mineral density (BMD) of the lumbar spine and femoral neck increased significantly (by 23% and 14%, respectively), but peripheral quantitative computed tomography at the ultradistal radius revealed no gain of either trabecular or cortical volumetric BMD. The increase in areal BMD was thus driven by an increase in bone size. Indeed, longitudinal bone growth (height, +8.5%) and especially cross-sectional area of the radius (+46%) and cortical thickness (+12%), as measured by peripheral quantitative computed tomography, increased markedly during estrogen treatment. These findings demonstrate that androgens alone are insufficient, whereas estrogens are essential for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype.     

Magnetic resonance imaging identifies early femoral head ischemic necrosis in patients receiving systemic glucocorticoid therapy

Ischemic necrosis of bone, a frequent complication of glucocorticoid therapy, can result in disability due to bone collapse and destruction. Some investigators have suggested that core decompression of involved marrow benefits patients with early disease. As radiographs are normal in early disease, identification of patients has been dependent on nonspecific radionuclide imaging or more specific but invasive hemodynamic studies. In order to define a sensitive, noninvasive diagnostic tool, we compared magnetic resonance imaging (MRI) to 99mtechnetium diphosphonate and 99mtechnetium sulfur colloid scintigraphy in 10 consecutive glucocorticoid treated patients with suspected femoral head ischemic necrosis of bone but normal roentgenograms. MRI identified the ischemic necrosis (defined by characteristic radiographic progression or histology) in 13/13 femoral heads. Both scans together identified only 5/13 of the cases. Only 1/20 osteoarthritic femoral heads had MRI patterns similar to those seen in ischemic necrosis of bone. We conclude that MRI is a sensitive and relatively specific method to detect early femoral head ischemic necrosis of bone.     

Bone scintigraphy equipped with a pinhole collimator for diagnosis of avascular necrosis of the femoral head

Summary The objective was to compare the sensitivities for diagnosis of avascular necrosis of the femoral head of bone scintigraphy equipped with a pinhole collimator and with an high resolution parallel collimator. Bone scintigraphy equipped with a pinhole collimator and with an high resolution parallel collimator were performed in 16 patients with bilateral (n=7) or unilateral (n=9) avascular necrosis of the femoral head. Bone scintigraphy equipped with a pinhole collimator documented a photopenic defect in 78.3% of the necrotic hips, while bone scintigraphy equipped with an high resolution parallel collimator documented a defect in 47.8%. There was no false-positive diagnosis of avascular necrosis of the femoral head on either bone scintigraphy equipped with a pinhole or with an high resolution parallel collimator. In conclusion, bone scintigraphy equipped with a pinhole collimator has a greater sensitivity for diagnosis of avascular necrosis of the femoral head than bone scintigraphy equipped with an high resolution parallel collimator.     

Cushing''s disease presenting with avascular necrosis of the femoral heads and complicated by pituitary apoplexy.

A case of Cushing's disease presenting with avascular necrosis of the femoral heads is described. Eighteen months after the onset of hip symptoms the patient developed pituitary apoplexy and presented to hospital as a medical emergency. Endogenous hypercortisolism is a rare and important cause of avascular necrosis of bone.     

Female pseudohermaphroditism and inefficient peak bone mass in an untreated subject affected by 21-hydroxylase congenital adrenal hyperplasia

Here we describe a subject with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-CAH), in its classical virilizing form, who presented at birth ambiguous genitalia and subsequently was assigned by the parents as male. At the age of 8 years, he underwent a two-step surgical correction of hypospadia and at 22 years old, uterus and ovaries were removed and a bilateral testicular prothesis was surgically placed in scrotum. He refused any chronic glucocorticoid therapy, that was given only acutely to prevent adrenal crises during stress, trauma surgery or severe illness. The patient is now 38 years old, he is genotypically female but phenotypically male, with high endogenous levels of androgen, all of adrenal origin, and with an apparent male sexual life. He had severe osteopenia, probably due to the lack of estrogen/androgen-induced increase in bone mineral density, although periferal estrogen conversion was normal. His skeletal mass, in fact, normally acquired during adolescence and early adult life, could in this case be inefficient, for the precocious pseudopuberty, that caused an inefficient peak bone mass in adolescence period.     

Sjögren's syndrome with bilateral spontaneous fracture of the femoral neck following aseptic necrosis of the femoral head

A woman with Sjögren's syndrome concurrently suffered bilateral fractures of the femoral neck without any proximate cause, while she had aseptic necrosis of the femoral head resulting from the treatment for Sjögren's syndrome. According to previous reports, fractures of the femoral neck following aseptic necrosis of the femoral head are attributed to primary diseases such as systemic lupus erythematosus (SLE) or idiopathic thrombocytopenic purpura (ITP), and steroids are administered in most cases. Heterogeneous bone regeneration after necrosis causes irregularity in its mechanical strength depending on which regions of frailty are generated. Patients with aseptic necrosis of the femoral head whose bone density is considerably reduced need careful medical attention to avoid fractures of the femoral neck caused by weak forces.     

Sjögren's syndrome with bilateral spontaneous fracture of the femoral neck following aseptic necrosis of the femoral head

Abstract

A woman with Sjögren's syndrome concurrently suffered bilateral fractures of the femoral neck without any proximate cause, while she had aseptic necrosis of the femoral head resulting from the treatment for Sjögren's syndrome. According to previous reports, fractures of the femoral neck following aseptic necrosis of the femoral head are attributed to primary diseases such as systemic lupus erythematosus (SLE) or idiopathic thrombocytopenic purpura (ITP), and steroids are administered in most cases. Heterogeneous bone regeneration after necrosis causes irregularity in its mechanical strength depending on which regions of frailty are generated. Patients with aseptic necrosis of the femoral head whose bone density is considerably reduced need careful medical attention to avoid fractures of the femoral neck caused by weak forces.     

Estrogen replacement therapy in a man with congenital aromatase deficiency: effects of different doses of transdermal estradiol on bone mineral density and hormonal parameters

The effects of different doses of transdermal estradiol (TE) on bone mineral density (BMD) in a man with aromatase deficiency were evaluated. The study protocol was divided in the following four phases: phase 1, before estradiol treatment; phase 2, 50 microg TE twice weekly for 6 months; phase 3, 25 microg TE twice weekly for 9 months; and phase 4, 12.5 microg TE twice weekly for 9 months. X-rays of hands, legs, and pelvis were performed, and BMD of the lumbar spine, hormonal parameters (LH, FSH, testosterone, and estradiol), and markers of bone turnover were determined during each phase. BMD in phase 1 was 0.933 g/cm2 and increased to 1.051 and 1.173 g/cm2 after 4 and 7 months of TE, respectively. In phase 3, BMD reached the maximum value (1.275 g/cm2). In phase 4, BMD decreased to 1.180 g/cm2 and was 1.029 g/cm2 at the end of the study protocol. A bilateral necrosis of femoral heads was also detected by x-ray films. In phase 1 serum testosterone was in the normal range, whereas serum estradiol was undetectable. During the 24-month period of treatment with TE (phases 2-4), estradiol was directly related to the amount of TE, whereas LH was inversely related to estradiol serum levels. Estradiol and gonadotropins reached optimal values only in phase 3, when FSH also was near normal; serum testosterone concentrations were normal in phases 3 and 4. This study confirms the role of estrogens in achieving and maintaining bone mineral content in the human male, providing further clinical tools useful in the management of bone loss in aromatase deficiency in the male. We suggest that the adequate substitutive dose of TE for maintaining both bone mass and normal estradiol serum levels in adult men with aromatase deficiency may be 25 microg twice weekly (0.47 microg/kg weekly).     

Membrane-type matrix metalloproteinase-1 (MT1-MMP) is down-regulated in estrogen-deficient rat osteoblast in vivo

Our previous study showed that estrogen stimulates membrane-type matrix metalloproteinases-1 (MT1-MMP) production in osteoblastic cells culture, but has no effect on MMP-2 and TIMP-2 synthesis. Osteoblast-derived MT1-MMP have been recently implied to play a role in bone metabolism by degrading tumor necrosis factor-alpha (TNF-alpha), resolving extracellular matrix and activating proMMP-2, which requires the process of activation mediated by MT1-MMP/tissue inhibitor of metalloproteinase (TIMP-2) complex on the cell surface. To investigate the mechanism of bone loss following estrogen deficiency, we examined the effects of estrogen on osteoblast synthesis of MT1-MMP, MMP-2 and TIMP-2. In situ hybridization and immunohistochemistry of rat bone samples were used to document the synthesis of MT1-MMP, MMP-2, and TIMP-2 mRNA and protein. Osteoblasts from distal femoral head showed an increase in the pattern of MT1-MMP mRNA and protein production in sham-operated controls and 17beta-estradiol (E2)-treated rats, compared with the ovariectomized group; the synthesis of MMP-2 and TIMP-2 mRNA and protein was unaffected. Our data show a down-regulation of MT1-MMP synthesis by osteoblast in vivo following estrogen withdrawal, and treatment with E2 resulted in induced MT1-MMP expression in vivo. There is evidence suggesting a role for MT1-MMP in the process of bone loss during the pathogenesis of osteoporosis.     

A case of SLE with bilateral osteonecrosis of femoral heads and bone infarct in distal of femur

Osteonecrosis of bone is a major cause of morbidity in lupus patients, and is most common in the femoral head. It has been reported in wide range of patients (2–30%). In different studies presence of arthritis, Raynaud phenomenon, vasculitis, pleuritis, antiphospholipid and other factors were associated with this occurrence. Bone infarcts were also associated with these factors. We report a 21-year-old patient who was diagnosed as SLE about 3 years ago. When the patient was stable with hydroxychloroquine and prednisolone referred to rheumatologic clinic for mechanical knee pain, in evaluation she had bone infarct in distal femur. Two months later she came back with bilateral hip pain, and in evaluation she had bilateral osteonecrosis of femoral heads. There are many reports of femoral head osteonecrosis in lupus patients, and also one report of multiple bone infarct and pain in SLE, but we did not find any report of these two phenomena together in a patient whose disease was controlled and she took minimum of steroid and DMARD in the about 2-month follow-up, and this was very interesting for us.     

Aseptic necrosis of both femoral heads as first symptom of chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a disease of the elderly; in rare cases it occurs in childhood or adolescence. One complication at primary diagnosis is leukostasis, which usually causes respiratory, retinal, or central nervous symptoms. In this report we describe the case of a 24-year-old woman who developed aseptic necrosis of both femoral heads, which was successfully treated by bore holes in the femoral heads. This is a very rare complication of severe leukostasis, leading to the diagnosis of CML in this case. To our knowledge, this is the first case of an adult patient showing aseptic necrosis of femoral heads caused by leukostasis.     

Osteoporosis: gender differences and similarities.

Although osteoporosis has traditionally been considered a disease of women, men also incur substantial bone loss with aging, and elderly men have age-specific hip fracture incidence rates and vertebral fracture prevalence rates that are at least half those in women. Early postmenopausal bone loss (which results in the syndrome of type I osteoporosis) is due to the direct skeletal consequences of estrogen deficiency, manifested by an increase in bone resorption without an adequate increase in bone formation. Recent evidence indicates that even late postmenopausal bone loss (type II or 'smile' osteoporosis) in women may be due to estrogen deficiency. In particular, the late consequences of estrogen deficiency in elderly women result in abnormalities in calcium homeostasis and increases in parathyroid hormone secretion, leading to increased bone resorption and bone loss. The etiology of bone loss in aging men has remained relatively unclear. Recent evidence from a male deficient in estrogen receptor-alpha and in two males with aromatase deficiency indicate that estrogen may play a significant role in bone metabolism in men. Moreover, several large epidemiologic studies have found that bone mineral density correlates better with serum estrogen than testosterone in aging men. Thus estrogen deficiency may lead to bone loss in men.     

Steroid induced early changes of the femoral head in man--histological study of autopsied cases

High dose corticosteroid therapy constitutes one of major causes of osteonecrosis of the femoral head. To examine the early changes of the femoral head induced by corticosteroid therapy, 20 femoral heads were obtained at autopsy and the other 19 femoral heads without having been on steroid were served as controls. Histological examination from steroid treated group revealed that in areas of subchondral bone there were observed necrotic changes of osteocytes. The nucleus was so pressed to one side of the cell as to assume crescent like aspect. When stained with Sudan IV, fat positive materials were found in the osteocyte lacunae. Electron micrographic examination revealed intracellular fat as low electron dense droplets in these degenerative osteocytes. Examination of bone marrow showed an increase of the number of fat cells in steroid treated group. These changes in man may represent some failure in lipid metabolism, although it is unknown whether these events may produce osteonecrosis of the femoral heads.     

Ischemic necrosis of bone in systemic lupus erythematosus.

Twenty-three patients with systemic lupus erythematosus (SLE) and ischemic bone necrosis are reported. All patients had received corticosteroids prior to the onset of ischemic necrosis, although one patient had received none for 13 years previously. Nineteen (83%) patients had multiple bone lesions including the femoral heads in 21 (91%) which were bilaterally involved in 15. In addition, humeral heads were affected in seven patients and the tibial plateaus, in three. The most striking feature of this group was the high incidence of Raynaud's phenomemon present in 14 (61%) of the 23 patients. Furthermore, central nervous system involvement was present in 10 (43%) patients, more prominent in those without Raynaud's (67%) than in those with vasospasm (29%). Thus, 20 of the 23 patients, or 87%, evidenced vascular abnormalities either in the form of Raynaud's phenomenon and/or systemic vasculitis.The pathogenesis of ischemic bone necrosis is discussed. In SLE, vasospasm or vasculitis, or both, augmented by corticosteroid therapy, could impede the microcirculation and result in the ischemic lesion.     

The Impact of congenital,severe, untreated growth hormone (GH) deficiency on bone size and density in young adults: insights from genetic GH-releasing hormone receptor deficiency

GH and IGF-I have well recognized effects on bone elongation during development, but their importance for bone mineralization and structure during the growth phase are less well understood. Because children with GH deficiency are generally treated with GH, little detailed information exists in humans about the effects of long-term GH deficiency on bone development. The recently described syndrome of genetic GHRH receptor deficiency in Pakistan (dwarfism of Sindh) affords a unique opportunity to examine the question of GH deficiency on bone development because the affected patients have congenital, severe, isolated GH deficiency, which had never been treated because of societal reasons. We performed dual energy x-ray absorptiometry scans in four adult males (age, 23-30 yr) to address the question of bone mineralization. Areal bone mineral density (BMD) was low (mean Z scores: -3.3, -2.1, -3.7, and -1.7) in the lumbar spine, femoral neck, forearm, and total skeleton, respectively. This low areal BMD is in part caused by the small bone size in these dwarfed patients. When corrected for size, volumetric BMD (bone mineral apparent density) was normal to near normal (mean Z scores: -1.2, +0.8, and +0.8 for lumbar spine, femoral neck and total skeleton, respectively). We conclude that GH/IGF-I deficiency has relatively little impact on bone mineralization during the bone accretion phase. This is in marked contrast to their effect on bone elongation and overall bone size.     

Calcitonin and estrogens

Estrogen deficiency is thought to be the main factor leading to postmenopausal osteoporosis (PMO). A role for calcitonin (CT) has been proposed as mediator of estrogen action on bone, and therefore, as pathogenetic factor of PMO. However, this hypothesis is still controversial. To further analyze the relationships between estrogens and CT in PMO, we studied the effects of one-year estro/progesterone therapy on CT secretory reserve, evaluated by a calcium infusion test in 12 postmenopausal women, as compared to 12 placebo treated subjects. In the hormone treated group, blood levels of CT showed a progressive increase during the study and a plateau was reached at 9 months, indicating that CT production achieved a new steady state. Hormonal therapy also significantly improved the CT response to calcium stimulation test. A concomitant increase of vertebral bone mass was observed in the hormone treated women, who also maintained initial bone density of femoral dyaphyses. On the contrary, the placebo treated group continued to lose bone mineral at both sites. Our study demonstrates that estrogens regulate CT secretion in postmenopausal women; thus, CT may be considered a mediator of estrogen action on bone.     

雌激素缺乏对大鼠股骨骨髓细胞Fas、FasL表达的影响

目的探讨去势后SD大鼠骨质疏松发生过程中股骨骨髓细胞Fas、FasL的表达情况。方法建立绝经后骨质疏松模型（去势组，切除双侧卵巢）。用免疫组织化学方法（SABC法）检测不同时期去势大鼠与正常大鼠股骨骨髓细胞Fas、FasL的表达情况。结果在SD大鼠去势后骨质疏松发生过程中股骨骨髓细胞Fas、FasL的表达呈现出下降的趋势，并且破骨样前体多核细胞都呈弱阳性表达；而非去势组大鼠股骨骨髓细胞Fas、FasL呈强阳性表达，并且这种强阳性的表达多局限于破骨样前体多核细胞的胞浆中。结论在雌激素缺乏的情况下，骨髓细胞Fas、FasL的表达减弱；雌激素能加强骨髓破骨样前体多核细胞Fas、FasL的表达，从而引起骨髓中破骨样前体多核细胞凋亡的发生。     

Amenorrhea in young women

The adolescent is an important period in which the peak bone mass is acquired. A sufficient attainment of peak bone mass is important as well as a prevention of bone loss in postmenopausal period in order to prevent osteoporosis in future. It is well known that the estrogen deficiency is at risk of developing osteopenia. Anorexia nervosa, excessive exercises, Turner's syndrome and premature ovarian failure are leading causes of prolonged amenorrhea in young women. However, estrogen deficiency is not the only cause of low bone mass in these women. Although hormone replacement therapy is effective to increase bone mineral density in these women, management of amenorrhea should be individualized according to the status of bone metabolism.