Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis

The efficacy of ipriflavone was investigated in a 1-year double-blind, placebo-controlled, parallel group clinical trial. Ninety-one postmenopausal women completed the study, 41 received ipriflavone and 50 placebo treatment. After six months the bone mineral density of the L2-L4 vertebral region increased in the ipriflavone-treated group (0.015 g/cm2), whereas it decreased in the placebo-treated group. The differences between the treatment groups were statistically significant. Our results support the efficacy of ipriflavone in the treatment of postmenopausal osteoporosis. Since the positive effect was more pronounced after 6 months, the possibility of an intermittent ipriflavone treatment might be taken into consideration in the future.     

Role of hormonal factors in the pathogenesis of postmenopausal osteoporosis

In 47 women with postmenopausal osteoporosis, pretreatment studies by microradiography, radioimmunoassay and other methods showed increased bone resorption, normal bone formation, and decreased serum immunoreactive parathyroid hormone (PTH). In patients treated with a physiologic replacement dose of estrogen, bone resorption decreased to normal and PTH increased after short-term therapy; bone formation decreased to very low levels after long-term therapy. These data indicate that, in most patients, both an intrinsic abnormality of bone cell function and a disruption of the normal regulation of bone turnover by PTH and sex hormones, as a result of the menopause, are important in the pathogenesis of osteoporosis.     

Evaluation and treatment of postmenopausal osteoporosis

OBJECTIVES: To review the recent literature and develop a logical strategy with which to approach the diagnosis and treatment of osteoporosis, based on clinical evidence and accepted practices. METHODS: Published reports from 1983 through 1997 obtained by MEDLINE search were reviewed and analyzed by both authors. RESULTS: Osteoporosis is a widespread medical condition readily identifiable by current diagnostic modalities, including quantitative computed tomography, single and dual x-ray absorbtiometry, radio-absorbtiometry, and ultrasound. Properly implemented prevention and treatment strategies, such as calcium and vitamin D supplementation, exercises, hormone replacement therapy, alendronate, and calcitonin, may reduce the future fracture risk in many individuals. An algorithm is provided based on currently available clinical evidence for the evaluation and treatment of osteoporosis. CONCLUSIONS: Expanded use of currently available and emerging diagnostic and therapeutic modalities should lead to decreased fracture rates and a resultant increase in quality of life for patients with osteoporosis.     

Prevention and treatment of postmenopausal osteoporosis

The purpose of the review is to outline the interventions, both pharmacological and non-pharmacological, available to prevent postmenopausal osteoporosis (PMO) and treat the established disease. Current suggested guidelines for the most cost-effective treatment and prophylactic strategies are included following a consideration of the available options. As life expectancy has increased so has the incidence of PMO which has major quality of life implications for the sufferers and economic implications for the authorities responsible for their treatment. PMO represents a significant public health problem and although more effective treatments are becoming available prevention of the disease by taking account of existing risk factors is preferable. Indeed, a population approach to prevention may be more cost effective than screening for the disease. Attention to dietary calcium intake and exercise regimes have been shown to be effective prophylactic measures premenopausally, while the treatment of choice is hormone replacement therapy (HRT). HRT treats other postmenopausal symptoms in addition to PMO and is available in many presentations, containing different hormones, at different doses intended for different routes of administration. The optimum treatment duration is controversial and may contribute to some of the risks associated with HRT such as endometrial and breast carcinoma and venous thromboembolism (VTE). Newer effective treatments include the bisphosphonates and novel formulations of calcitonin, but older approaches such as vitamin D, anabolic steroids and fluoride are still utilised in some circumstances. However, most promise has been shown by synthetic hormonal modulators currently being trialled.     

Biochemical markers of bone remodeling in the prevention of postmenopausal osteoporosis]

Normal bone mass is one of the principal factors in the prevention of osteoporosis for women in advanced age. Therefore, it is necessary to have efficacious serum and urinary markers available to screen the bone development and the bone resorption. Even if we are also far from identifying an ideal marker, the measurement of some substances such as pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) seems to be a first progress for efficacious and rather simple techniques.     

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.     

Glucocorticoid-induced osteoporosis: prevention and treatment

Glucocorticoid excess carries the risk of inducing secondary osteoporosis. In endogenous Cushing's syndrome, osteoporosis may be the presenting symptom of the underlying disease. Bone loss may reverse after the condition is cured, but often active treatment of established osteoporosis is necessary. In long-term glucocorticoid treatment at therapeutic doses, bone loss is likely and should be prevented; if prevention is ineffective, treatment is necessary. Hypercortisolism impairs calcium homeostasis and bone metabolism in a complex, multifactorial way: Glucocorticoids diminish calcium absorption and increase renal calcium excretion; this negative calcium balance leads to secondary hyperparathyroidism and osteoclast activation. Osteoblast activity is directly impaired by glucocorticoids, which lower activity of the gonadal hormone axis so that hypogonadism also contributes to bone loss. Glucocorticoids lead to muscle atrophy and decreased muscle strength with negative consequences for bone formation. For prevention and treatment, two different strategies have been used. The pathophysiological approach substitutes calcium and vitamin D in the first step; if bone loss nevertheless continues, bone formation is stimulated by fluorides. The alternative pharmaco-dynamic approach uses antiresorptives-calcitonin or, for preference, bisphosphonates. Clinically it is mandatory to monitor all patients in whom glucocorticoids are used (e.g., organ transplant recipients) before and after the initiation of treatment to stabilize bone metabolism as early as possible.     

The role of apoptosis in the pathogenesis and treatment of diseases

In adult multicellular organisms, homeostasis is determined in each cell lineage by a balance between cell death and cell growth. Dysregulation of cell death mechanisms is involved in the pathogenesis of an increasing number of diseases. Defective apoptosis can participate in malignant transformation, viral latency and autoimmune diseases. Excessive apoptotic cell death is involved in CD4+ T-cell depletion observed in acquired immune deficiency syndrome, in fulminant hepatitis associated with infection by hepatitis B and C viruses, in some neurodegenerative disorders and haematological diseases, in polycystic kidney disease and ischaemia. Three steps can be distinguished in the pathway that leads to cell death. The first step involves interactions between the extracellular and intracellular signals that decide whether a cell should live or die. When death is chosen, a common pathway that involves at least the Bcl-2- family of proteins and the interleukin-1 beta (IL-1 beta)-converting enzyme-related cysteine proteases confirms whether or not the cell should die. Finally, if death is allowed to occur, the apoptotic process itself is characterized by deoxyribonucleic acid (DNA) fragmentation, proteolysis and morphological changes that precede the engulfment of apoptotic cells by neighbouring cells and phagocytes. Several inducers and inhibitors of apoptosis acting on one or several of these three steps that characterize the apoptotic process have been identified in vitro. Their potential usefulness in improving the current therapeutic strategies and designing new strategies in several different diseases is discussed.     

The federal role in research, treatment, and prevention of alcoholism.

Outlines the dimensions of the alcohol abuse problem in the US, federal legislation related to the treatment and prevention of alcohol and drug abuse, and priorities for future government involvement in research and treatment. It is argued that the government should play a greater role in the dissemination of research results; fund demonstration projects targeted at improving the effectiveness of alcoholism treatment; coordinate employee assistance programs in the workplace; and ensure that services are extended to currently underserved populations such as the elderly, minorities, and women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Small bone-building fragments of parathyroid hormone: new therapeutic agents for osteoporosis

The brittle, fracture-prone bones of an osteoporotic postmenopausal woman are the products of an excessive uncompensated resorption of trabecular bone by osteoclasts. Osteoporosis is currently treated with the osteoclast suppressors calcitonin, bisphosphonates, or oestrogen, which stop further bone resorption without stimulating new bone growth. Here, James Whitfield and Paul Morley review the growing evidence that small adenylate cyclase-stimulating fragments of the parathyroid hormone are promising therapeutic agents for osteoporosis that potently stimulate osteoblasts to make mechanically strong or supranormally strong bone.     

DNA analysis for prevention and treatment of osteoporosis

No prior studies have evaluated the relationship between the site of right ventricular stimulation, the site of prior infarction, and the inducibility of ventricular tachycardia (VT). This study was performed to determine if the location of pathologic Q waves influences the inducibility of VT at various right ventricular sites in patients with coronary artery disease (CAD) and a history of myocardial infarction (MI). In 30 patients with a history of sustained, monomorphic VT, CAD, prior MI, and pathologic Q waves, programmed ventricular stimulation was performed at the right ventricular apex, septum, and outflow tract, in random order. There was electrocardiographic evidence of an MI that was inferior in 11 patients, anterior in 10 patients, and both inferior and anterior in 9 patients. Sustained, monomorphic VT was induced in 27 of 30 patients (90%). There were no significant differences among the three sites in the rate of inducibility of VT. The rate of inducible VT at each of the three right ventricular sites was not affected by the location of prior infarction. In conclusion, among patients with sustained, monomorphic VT, CAD, and a history of MI, the incidence of inducible sustained, monomorphic VT is not influenced by the location of prior infarction, regardless of whether programmed ventricular stimulation is performed at the right ventricular apex, septum, or outflow tract.     

Estrogen treatment for prevention and therapy of osteoporosis

Postmenopausal osteoporosis affects 30% of all women. Major risk factors include hereditary factors, deficiency of calcium and vitamin D in the diet, too little exercise, excessive alcohol consumption and a reduction in the amount or duration of sex hormone secretion (late menarche, early climacterium, etc.). Osteoporosis prophylaxis is of great importance. Since in the early stages, osteoporosis does not produce symptoms, an early diagnostic work-up involving osteodensitometry makes good sense in patients with individual risk factors. In addition to physical activity, basic countermeasures always include adequate calcium and vitamin D supplementation. Replacement therapy with estrogens (usually in combination with gestagens) is an effective and causal treatment of postmenopausal osteoporosis. However, the indication must be established individually on the basis of a benefit-risk consideration.     

A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis

The aim of this study was to investigate the extent of natural intrinsic fluorescence in carious human dentine and any correspondence of such autofluorescence (AF) to the mineral distribution within the lesion. Two investigative techniques were used, both employing the same sample set and fields in diamond-polished block surfaces of polymethylmethacrylate-embedded carious teeth. AF at emission wavelengths >515 nm, excited by 488-nm laser light, was assessed using a confocal laser scanning optical microscope (CLSM), the recordings made under standard operating conditions. The relative mineral content was assessed using digital backscattered scanning electron microscopy (20 kV BSE-SEM). The AF intensity correlated with the level of demineralisation as seen by BSE, but the depth of the lesion as seen by CLSM was significantly greater implying that the AF is not directly related to the mineral component.