Thymulin stimulates prolactin and thyrotropin release in an age-related manner

Reduction in the biomechanical competence of the axial skeleton can result in challenging complications. Osteoporosis consists of a heterogeneous group of syndromes in which bone mass per unit volume is reduced in otherwise normal bone, which results in more fragile bone. The geriatric population has an increased risk for debilitating postural changes because of several factors. The two most apparent factors are involutional loss of functional muscle motor units and the greater prevalence of osteoporosis in this population. Obviously, the main objective of rehabilitation is to prevent fractures rather than to treat the complications. These complications can vary from "silent" compression fractures of vertebral bodies, to sacral insufficiency fractures, to "breath-taking" fractures of the spine or femoral neck. The exponential loss of bone at the postmenopausal stage is not accompanied by an incremental loss of muscle strength. The loss of muscle strength follows a more gradual course and is not affected significantly by a sudden hormonal decline, as is the case with bone loss. This muscle loss may contribute to osteoporosis-related skeletal disfigurations. In men and women, the combination of aging and reduction of physical activity can affect musculoskeletal health, and contribute to the development of bone fragility. The parallel decline in muscle mass and bone mass with age is more than a coincidence, and inactivity may explain some of the bone loss previously associated with aging per se. Kyphotic postural change is the most physically disfiguring and psychologically damaging effect of osteoporosis and can contribute to an increment in vertebral fractures and the risk of falling. Axial skeletal fractures, such as fracture of the sacral alae (sacral insufficiency fracture) and pubic rami, may not be found until radiographic changes are detected. Management of chronic pain should include not only improvement of muscle strength and posture but also, at times, reduction of weight bearing on the painful pelvis with insufficiency fractures. Axial skeletal health can be assisted with improvement of muscular supportive strength. Disproportionate weakness in the back extensor musculature relative to body weight or flexor strength considerably increases the risk of compressing porous vertebrae. A proper exercise program, especially osteogenic exercises, can improve musculoskeletal health in osteoporotic patients. Exercise not only improves musculoskeletal health but also can reduce the chronic pain syndrome and decrease depression. Application of a proper back support can decrease kyphotic posturing and can expedite the patient's return to ambulatory activities. Measures that can increase safety during ambulatory activities can reduce risk of falls and fractures. Managing the musculoskeletal challenges of osteoporosis goes hand in hand with managing the psychological aspects of the disease.     

Corticosteroid osteoporosis in the adult]

EARLY BONE LOSS: Bone loss is greatest in patients given supra-physiological doses of corticosteroids during the first months of treatment. The rate of loss then tapers off but persists throughout the duration of the treatment because of depressed osteoblast activity. EVALUATE THE RISK: Corticosteroid-induced osteoporosis is a multifactorial phenomenon depending in part on the duration and the dose of the treatment and in part on prior bone status and the causal disease. Young subjects can expect to recover bone mass partially or completely after withdrawal. Menopaused women not taking hormone replacement therapy have a low bone mass and are high risk patients. PREVENTION: Preventive measures against corticosteroid-induced osteoporosis should begin with treatment onset. Patients should be given calcium and vitamin D supplements, hormone replacement therapy (menopaused women) or androgens (hypogonadic men), and biphosphonates (for young patients at risk or in case of bone mass despite the preceding measures).     

Differential osteoporosis diagnosis in the woman

Bone mineral density of a woman in the second half of her life depends on the amount of bone made during growth and its subsequent rate of loss. Although the rate of bone loss did receive more attention in the study of pathogenesis of osteoporosis, it is becoming increasingly clear that insufficient accumulation of skeletal mass by young adulthood predisposes a person to low bone mass and subsequently to fractures later in life as age related and menopause-related bone loss ensue. In this article we 1) explain the role of inadequate peak bone mass as a major risk factor for osteoporosis and 2) give an overview of factors leading to osteoporosis by decreasing bone mass. Special emphasis has been put on iatrogenic osteoporosis which is frequently neglected because of the fact that the responsible agents often are not known as to be deleterious to the skeleton: among others, glucocorticoids, thyroid hormones and antiepileptics adversely affect bone.     

Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis

BACKGROUND: Small increases in bone mass are commonly seen with existing treatments for osteoporosis, which reduce bone remodelling and primarily prevent bone loss. Since these drugs reduce but do not eliminate risk of fractures, an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed. METHODS: We did a 3-year randomised controlled trial to find out the effects of 1-34 human parathyroid hormone (hPTH [1-34], 400 U/25 micrograms daily subcutaneously) in postmenopausal women with osteoporosis taking hormone-replacement therapy (n = 17). The controls were women taking hormone-replacement therapy only (n = 17). The primary outcome was bone-mineral density of the lumbar vertebrae, with bone-mineral density at other sites and vertebral fractures as secondary endpoints. FINDINGS: Patients taking hormone-replacement therapy and PTH (1-34) had continuous increase in vertebral bone-mineral density during the 3 years, whereas there was no significant change in the control group. The total increase in vertebral bone-mineral density was 13.0% (p < 0.001); 2.7% at the hip (p = 0.05); and 8.0% in total-body bone mineral (p = 0.002). No loss of bone mass was found at any skeletal site. Increased bone mass was associated with a reduction in the rate of vertebral fractures, which was significant when fractures were taken as a 15% reduction in vertebral height (p = 0.04). During the first 6 months of treatment, serum osteocalcin concentration, which reflects bone formation, increased by more than 55%, whereas excretion of crosslinked n-telopeptide, which reflects bone resorption, increased by only 20%, which suggests some uncoupling of bone formation and resorption. By 6 months, there were similar increases in both markers, which gradually returned towards baseline as the study progressed. Vertebral bone-mineral density increased most during the first year of PTH treatment. INTERPRETATION: We found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone-replacement therapy. PTH also increases total-body bone mineral, with no detrimental effects at any skeletal site. The increased vertebral mass was associated with a reduced rate of vertebral fracture, despite increased bone turnover. Bone-mass changes may be consistent with a reduction in all osteoporotic fractures. If confirmed in larger studies, these data have important implications for the treatment of postmenopausal osteoporosis.     

Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group

BACKGROUND: Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. METHODS: Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration > or = 12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. RESULTS: Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P < 0.001), and the reduction was evident in both stratum 1 (P = 0.04) and stratum 2 (P = 0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was tolerated well. CONCLUSIONS: Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma.     

Effects of synthetic salmon calcitonin and alendronate on bone quality in ovariectomized rats

BACKGROUND: The aim of this study was to assess the effect of calcitonin (CCT) and alendronate (ALN) on bone quality through histomorphometric, histological, densitometric and crystallographic evaluations in an experimental model of osteoporosis obtained in ovariectomized rats. METHODS: The animals were randomly assigned to the treatment with CCT (2 IU/kg/day, N-12) or with ALN (6 micrograms/kg/day, N-12) given subcutaneously, starting three months after ovariectomy: treatment lasted 60 days. Six rats untreated after ovariectomy and other 6 non ovariectomized (intact) were taken as controls. At the end of treatment the animals were sacrificed and femurs explanted for laboratory examinations. Results were evaluated by an ANOVA followed by the Tukey's test when appropriate. RESULTS: The histomorphometric analysis showed a significant increase of the trabecular bone volume and of the cortical bone thickness either with CCT and ALN in comparison with the ovariectomized untreated controls. Optic and electronic microscopy examinations suggest a higher bone remodeling after ALN than after CCT, but accompanied by areas of imperfect mineralization, and more irregular osteon and collagen fibres disposition. The densitometry carried out at the femoral head and diaphysis showed a similar bone mass increase following either CCT and ALN, but significantly higher in comparison to the untreated controls. At the diaphysis level ALN was superior in increasing the bone mass also when compared to the intact rats. The mineralogic exams showed that CCT acted on the re-elaboration of the mineral phase approaching the molar ratio Ca/PO4 to the physiological values typical of senescence, and crystallography revealed that the formation of hydroxyapatite crystals follows a physiological mineral redeposition: those phenomena were not observed for ALN. CONCLUSIONS: In conclusion both CCT and ALN could reduce the bone loss due to osteoporosis, by increasing the bone mass and thickness. Nevertheless the submicroscopic and chemical bone structure are less similar to the physiologic ones after treatment with ALN.     

Growth hormone and bone

It is well known that GH is important in the regulation of longitudinal bone growth. Its role in the regulation of bone metabolism in man has not been understood until recently. Several in vivo and in vitro studies have demonstrated that GH is important in the regulation of both bone formation and bone resorption. In Figure 9 a simplified model for the cellular effects of GH in the regulation of bone remodeling is presented (Fig. 9). GH increases bone formation in two ways: via a direct interaction with GHRs on osteoblasts and via an induction of endocrine and autocrine/paracrine IGF-I. It is difficult to say how much of the GH effect is mediated by IGFs and how much is IGF-independent. GH treatment also results in increased bone resorption. It is still unknown whether osteoclasts express functional GHRs, but recent in vitro studies indicate that GH regulates osteoclast formation in bone marrow cultures. Possible modulations of the GH/IGF axis by glucocorticoids and estrogens are also included in Fig. 9. GH deficiency results in a decreased bone mass in both man and experimental animals. Long-term treatment (> 18 months) of GHD patients with GH results in an increased bone mass. GH treatment also increases bone mass and the total mechanical strength of bones in rats with a normal GH secretion. Recent clinical studies demonstrate that GH treatment of patients with normal GH secretion increases biochemical markers for both bone formation and bone resorption. Because of the short duration of GH treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. Interestingly, GH treatment to GHD adults initially results in increased bone resorption with an increased number of bone-remodeling units and more newly produced unmineralized bone, resulting in an apparent low or unchanged bone mass. However, GH treatment for more than 18 months gives increased bone formation and bone mineralization of newly produced bone and a concomitant increase in bone mass as determined with DEXA. Thus, the action of GH on bone metabolism in GHD adults is 2-fold: it stimulates both bone resorption and bone formation. We therefore propose "the biphasic model" of GH action in bone remodeling (Fig. 10). According to this model, GH initially increases bone resorption with a concomitant bone loss that is followed by a phase of increased bone formation. After the moment when bone formation is stimulated more than bone resorption (transition point), bone mass is increased. However, a net gain of bone mass caused by GH may take some time as the initial decrease in bone mass must first be replaced (Fig. 10). When all clinical studies of GH treatment of GHD adults are taken into account, it appears that the "transition point" occurs after approximately 6 months and that a net increase of bone mass will be seen after 12-18 months of GH treatment. It should be emphasized that the biphasic model of GH action in bone remodeling is based on findings in GHD adults. It remains to be clarified whether or not it is valid for subjects with normal GH secretion. A treatment intended to increase the effects of GH/IGF-I axis on bone metabolism might include: 1) GH, 2) IGF, 3) other hormones/factors increasing the local IGF-I production in bone, and 4) GH-releasing factors. Other hormones/growth factors increasing local IGF may be important but are not discussed in this article. IGF-I has been shown to increase bone mass in animal models and biochemical markers in humans. However, no effect on bone mass has yet been presented in humans. Because the financial cost for GH treatment is high it has been suggested that GH-releasing factors might be used to stimulate the GH/IGF-I axis. The advantage of GH-releasing factors over GH is that some of them can be administered orally and that they may induce a more physiological GH secretion. (ABSTRACT TRUNCATED)     

Bone mass and ageing

Bone can be divided into two kinds of tissue, cortical and trabecular bone. The skeleton comprises approximately 80% cortical bone, mainly in peripheral bones, and 20% trabecular bone, mainly in the axial skeleton. Bone density increases with skeletal growth to a peak in late adolescence or early adulthood. Bone loss subsequently occurs with ageing in both sexes, and in females accelerated loss occurs at the menopause. The risk of osteoporotic fracture in later life is the result of peak bone mass achieved at skeletal maturity and subsequent age-related and postmenopausal bone loss. Peak bone mass is largely genetically determined but is also influenced by environmental factors such as dietary calcium and physical activity. Bone loss with ageing occurs at different rates and different times in different skeletal sites. Femoral neck bone loss probably occurs in a linear fashion throughout life from early adulthood but may be accelerated at the menopause. Spinal bone loss may commence before the menopause but is rapidly increased in the immediate postmenopausal years. Bone strength is directly related to bone density, but the loading force is also relevant to risk of fracture.     

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.     

Disorders associated with clinically severe obesity: significant improvement after surgical weight reduction

BACKGROUND: Surgical treatment for patients with clinically severe obesity mainly aims to reduce morbidity. METHODS: Sixty-two patients were examined for disorders associated with morbid obesity before and after surgical weight reduction by vertical banded gastroplasty. All patients were followed-up for 12 to 48 months. RESULTS: At the end of the first postoperative year, 84% of the patients had lost at least 50% of their excess weight. Of the 218 weight-related pathologic conditions existing before the operation, 131 (60%) were completely cured, 50 (23%) showed significant improvement, and only 37 (17%) remained unchanged. The same percentages were obtained for patients followed tip for 24, 36, and 48 postoperative months. CONCLUSIONS: Surgical treatment of clinically severe obesity has a significant effect on the health of the patients by eliminating the associated disorders.     

Endolymphatic sac tumor: a case report and review of the literature

BACKGROUND: Papillary tumors of the temporal bone are very rare but aggressive neoplasms. In the past, a middle-ear origin was presumed. Only recently convincing evidence exists that these tumors in fact arise from the endolymphatic sac. METHODS: We present a case of an endolymphatic sac tumor (ELST) with detailed clinical, imaging, operative, and pathologic data. The literature on this rare tumor type is reviewed. RESULTS: This 63-year-old woman had a progressive mass lesion in the temporal bone for a period of more than 35 years, resulting in unilateral fifth to eleventh cranial nerve palsy, progressive ataxia, and a pyramidal and pseudobulbar syndrome. Computerized tomography (CT) and magnetic resonance imaging (MRI) showed a tumor invading the pars squamosa and petrosa of the temporal bone, and extending into the middle and posterior fossa. Angiography demonstrated a hypervascular tumor mass. The patient underwent surgery, with nonradical removal of a tumor. Histologic examination demonstrated a papillary ELST. A search through the literature revealed 36 patients with ELST, based on convincing anatomic and histologic considerations. CONCLUSIONS: It is important to make a distinction between ELST and the more benign middle-ear adenomas, since this leads to a different treatment and prognosis. ELST frequently invades the surrounding structures and extends intracranially. The treatment of choice is a radical resection, although complete resection is impossible in most of the cases. The value of adjunctive radiation therapy remains controversial.     

Bisphosphonates in bone diseases

Bisphosphonates are a class of drugs which are strongly attracted to the bone where they influence the calcium metabolism, mainly by inhibition of the osteoclast-mediated bone resorption. This property makes these compounds suited for the treatment of several diseases of the bone. In Paget's disease, several bisphosphonates can reduce bone pain and decrease the bone turnover 60-70%. Cyclical oral etidronate and daily oral alendronate both proved to reduce the vertebral fracture rate for postmenopausal osteoporotic woman, while most investigated bisphosphonates can increase spinal bone mass in osteoporosis. Bisphosphonates can help lowering serum calcium and reverse skeletal complications in malignancy mediated bone diseases. Oral and intravenous administration of therapeutic doses is relatively safe. In general, gastrointestinal disturbances are described most often and the oldest, least potent, bisphosphonate etidronate can induce osteomalacia. The various characteristics of bisphosphonates: physicochemical, biological, therapeutic and toxicological, vary greatly depending on the structure of the individual bisphosphonate. Even small changes in the structure can lead to enormous differences in potency. Overall, this class of drugs offers several prospects for the future.     

Risedronate

Risedronate is a pyridinyl bisphosphonate that can be administered orally in lower dosages than other antiresorptive bisphosphonates. Like others of its class risedronate inhibits osteoclast-mediated bone resorption. In experimental models of osteoporosis, risedronate inhibited bone loss and improved trabecular architecture. In patients with Paget's disease, pain diminished or disappeared and serum alkaline phosphatase levels decreased after treatment with oral risedronate 30 mg/day for < or = 3 months. Risedronate 30 mg/day orally for 2 months significantly reduced pain, whereas etidronate 400 mg/day orally for 6 months tended to reduce pain, in a randomised double-blind trial of patients with Paget's disease. Oral risedronate 5 mg/day for < or = 2 years increased bone mass in postmenopausal women with low or normal bone mass. Risedronate 2.5 mg/day prevented bone loss in postmenopausal women treated with glucocorticoids for rheumatoid arthritis. The incidence of gastrointestinal or other adverse events was similar in patients treated with risedronate or placebo in clinical trials.     

Pathologic features of spinal disorders in patients treated with long-term hemodialysis

STUDY DESIGN: Pathologic features of hemodialysis-associated spinal disorders were evaluated using preoperative radiographic images and histologic findings of the spinal lesions resected during surgery. OBJECTIVES: To investigate the pathology of hemodialysis-related spinal disorders and to determine the role of amyloidosis in the establishment of severe destruction of the spine. SUMMARY OF BACKGROUND DATA: The pathologic events leading to hemodialysis-associated spinal disorders are poorly understood. The distribution of amyloid deposits in the spine also has not been clarified. METHODS: Twenty patients with hemodialysis-associated spinal disorders were investigated regarding pathologic features of neural compression and spinal destruction. Preoperative radiographic images such as plain radiography, tomography, computed tomography, magnetic resonance imaging, and scintigraphy were assessed for the existence of an intracanal mass, hypertrophy of the ligamentum flavum, and destructive changes of the spinal components. Histologic examination also was conducted by light microscopy and scanning electron microscopy to determine the distribution pattern of amyloid deposits in the spinal components. RESULTS: Six patients with no destructive changes in the spine showed spinal canal stenosis. In the cervical spine, a main factor associated with spinal canal stenosis was the presence of intracanal amyloid deposits in three patients. In the lumbar spine, a main factor associated with spinal canal stenosis was hypertrophied ligamentum flavum in three patients. Destructive changes of the facet joints, intervertebral disc, and vertebral body were seen in the other 14 patients. Amyloid deposits were densely distributed at the enthesis of capsular fibers to the bone and in anular tears in the intervertebral discs. Vertebral end plates were destroyed by penetration of amyloid granulation into the vertebral body. Osteoclast activity in the destroyed vertebral bodies was enhanced, with no evidence of new bone formation. CONCLUSIONS: Amyloid deposits played an important role in the progression of spinal destruction and severe instability.     

Murine MPS I: insights into the pathogenesis of Hurler syndrome

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease resulting from deficiency of the lysosomal enzyme alpha-L-iduronidase. A murine model which shows complete deficiency in alpha-L-iduronidase activity has been developed and shows phenotypic features similar to severe MPS I in humans. Here we report on the long-term clinical, biochemical, and pathological course of MPS I in mice with emphasis on the skeletal and central nervous system (CNS) manifestations. Affected mice show a progressive clinical course with the development of coarse features, altered growth characteristics and a shortened life span. Progressive lysosomal accumulation is seen in all tissues. Skeletal manifestations represent the earliest clinical finding in MPS I mice with histologic analysis of growth plate and cortical bone revealing evidence that significant early pathology is present. Analysis of the CNS has revealed the novel finding of progressive neuronal loss within the cerebellum. In addition, brain tissue from MPS I mice shows increased levels of GM2 and GM3 gangliosides. This murine model clearly shows phenotypic and pathologic features which mimic those seen in severe human MPS I and should be an invaluable tool for the study of the pathogenesis of generalized storage disorders.     

Bone densitometry: patients receiving prolonged steroid therapy

Bone mass loss and osteoporosis are associated with various conditions, such as asymptomatic primary hyperparathyroidism, and treatments, such as prolonged steroid therapy. Bone densitometry is used to measure bone mass density to determine the degree of osteoporosis and to estimate fracture risk. Bone densitometers measure the radiation absorption by the skeleton to determine bone mass of the peripheral, axial, and total skeleton. Common techniques include single-photon absorptiometry (SPA) of the forearm and heel, dual-photon (DPA) and dual-energy x-ray absorptiometry (DXA) of the spine and hip, quantitative computed tomography (QCT) of the spine or forearm, and radiographic absorptiometry (RA) of the hand. Part I of this report addresses important technical considerations of bone densitometers, including radiation dose, site selection, and accuracy and precision, as well as cost and charges. Part II evaluates the clinical utility of bone densitometry in the management of patients receiving prolonged steroid therapy. Steroids have broad effects on both immune and inflammatory processes and have been used to treat a wide variety of immunologically mediated diseases. Osteoporosis and vertebral compression fractures have been considered major complications of prolonged steroid therapy. Bone loss is also a direct result of many of the diseases treated with steroids. Issues addressed are the type and extent of bone loss associated with steroid therapy, risk for fracture, whether steroid dose reduction or alternative therapy is an option, and whether osteoporosis associated with prolonged steroid use can be prevented or treated. The other assessments in this series address the clinical utility of bone densitometry for patients with: asymptomatic primary hyperparathyroidism, end-stage renal disease, vertebral abnormalities, and estrogen-deficient women.     

Cutaneous innervation and the role of neuronal peptides in cutaneous inflammation: a minireview

The patellofemoral joint is a complex articulation based on its dependence on both dynamic and static restraints for stability. Classification of patellofemoral disorders has been frought with confusion. However, progress has been made in the classification and understanding of these disorders by improved understanding of the biomechanics of the joint and by clarification of the terminology to describe patellofemoral pathology. The term chondromalacia patella, although once used as an all-inclusive term for anterior knee pain, is now widely accepted as a term used to describe pathologic lesions of the patellar articular cartilage found at arthroscopy or arthrotomy. An adequate classification system should aid in proper diagnosis and treatment of specific problems. If properly devised, it should also aid in the comparison of results between different treatment centers. In addition, it should be a system that is simple and useful in the clinical setting with minimal use of complicated imaging techniques. From a clinical perspective, patellofemoral problems in the skeletally mature patient fall into three broad categories: 1) patellofemoral instability, i.e., subluxation or dislocation; 2) patellofemoral pain with malalignment but no episodes of instability; and 3) patellofemoral pain without malalignment. The myriad of patellofemoral disorders then fall into subclassifications of these categories. Treatment algorithms can be broadly developed based on the general category, with specific treatments based on the subclassification. In this paper, the authors will present a review of the pertinent literature documenting patellofemoral classification systems and develop concepts of clinical classification of patellofemoral disorders based on the three categories described above.     

The Q-switched neodymium (Nd):YAG laser with quadruple frequency. Clinical histological evaluation of facial resurfacing using different wavelengths

The ovariectomized (OVX), lactating rat model has been used to investigate the skeletal effects of the plant estrogen, genistein, over a 14-day period. The OVX, lactating rat on a low-calcium diet loses slightly more than 50% of its bone mineral mass during the first 2 weeks of lactation, and we have demonstrated that estrogen treatment can significantly reduce the loss of femoral mass (ash weight). Following OVX, the rats were assigned to treatment or control groups (both placebo and positive control with estrogen replacement). The treatment groups received one of three doses of a genistein-rich preparation each day via the feed for 2 weeks, after which time the pups began to have an interest in solid feed. A positive control group received conjugated estrogen in the feed. The genistein doses were: low (0.5 mg/d); intermediate (1.6 mg/d); and high (5.0 mg/d). Measurements included ash weights of the femur, scanning electron microscopy (SEM) of the proximal tibia, and uterine weights. SEM results were as follows: (1) at the low dose genistein was approximately equally effective to estrogen in the retention of cancellous bone tissue, as reflected in the number and density of trabeculae in hemisections of the tibial subepiphyseal region, but at high doses genistein was less effective; and (2) rats treated with low-dose genistein, like estradiol, had rougher endosteal surfaces and smaller pores on these surfaces than untreated control rats. Mean ash weights of the entire femur were highest in the rats treated with the low dose compared to control rats (P < 0.05), and they were higher than ash weights of rats administered the intermediate or high doses of genistein. The mean ash weights of the femurs were consistent with the genistein effects on the tibias observed by SEM. In summary, a biphasic response to the genistein preparation was found in this OVX rat model. Interpretation of the results suggests that, at the low dose, genistein appears to be an agonist at the estrogen receptor locus, whereas at higher doses the genistein is less effective and may even have adverse effects on bone cells. These findings of a biphasic effect of genistein (i.e., an inverted U effect) are consistent with those of other recent reports in the literature on isolated bone cells and on reproductive tissues. In summary, lower doses of genistein from soy foods would be expected to act similarly to estrogens with a beneficial effect on bone tissue, but at high doses that are unlikely to be consumed in human diets, this soy derivative may have potentially adverse effects on bone cell functions and thereby on bone tissue.     

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.