物理治疗骨质疏松症的临床应用和机制研究

骨质疏松症是一种以骨量降低和骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨骼疾病,治疗方法主要有药物治疗和物理治疗。药物治疗效果确切但存在治疗周期长、依从性欠佳等问题。本文主要阐述物理治疗在骨质疏松症中的应用,并探索其可行性,为寻求适合我国骨质疏松人群的物理治疗方法提供依据。     

老年骨质疏松细胞病理特点与治疗思考

以往20～30年中骨质疏松症的治疗主要是抑制破骨细胞骨吸收,如双膦酸盐、降钙素和雌激素等一类药物,这些药物由于降低骨重建空间和延长骨矿化时间,对绝经后骨质疏松症可一定程度地增加骨密度和减少骨折危险性。然而抗骨吸收药物对老年骨质疏松症的治疗效果不尽理想,其原因除与老年人骨量丢失和骨结构改变程度较重有关外,还与对老年骨质疏松症的骨细胞病理特点认识尚不十分清楚,因而临床治疗缺乏老年人用药特点有关。近10多年来,本实验室以骨细胞衰老生物学为主要研究方向,对增龄过程中成骨细胞骨形成功能和破骨细胞骨吸收功能的变化规律作了…     

骨质疏松症及其骨折的局部治疗

骨质疏松症是一种以骨量减少和骨强度降低为表现的骨骼疾病,骨质疏松症患者骨折的风险性显著增加。每年大约有2000万人受到该种疾病的折磨。骨质疏松症是一种无声无息的疾病,往往不被重视和治疗,直到其引起骨折。该病目前主要的治疗手段仍有赖于系统用药以阻止骨密度和骨量的进一步丢失。骨质疏松症的局部治疗是一种新的治疗手段,其通过在易于发生骨质疏松性骨折的部位应用抗骨质疏松药物和促进骨形成的细胞因子或生物材料,达到提高局部骨质疏松骨的骨密度、改善骨微结构和生物力学性质的目的 。     

治疗骨质疏松症药物的研究进展

传统的骨质疏松类药物被分为骨吸收抑制药、骨形成促进药和骨矿化促进药。近年来,随着对该类药物研究的不断深入,更多的药物,如植物中的各种活性成分、锶制剂、护骨素等被应用于治疗骨质疏松症,取得了一定的疗效。本文简述了治疗骨质疏松症药物的研究进展。     

华法林引发骨质疏松症的发病机制及治疗策略

骨质疏松症是一种以骨矿物质含量低下、骨微结构损坏、骨强度降低、骨脆性增加、易发生骨折为主要特征的全身性骨代谢障碍性疾病。华法林可拮抗维生素K,使骨钙素的羧化受抑制,减少骨钙沉积,抑制骨矿化,从而干扰骨代谢,导致骨质疏松症或骨折,对于老年患者的影响尤其明显。长期服用华法林导致骨质疏松症的风险可能与用药剂量和时间相关。目前预防和治疗华法林引起的骨质疏松症主要依据原发性骨质疏松症的治疗原则,对于长期服用华法林的患者应补充钙剂和维生素D以预防骨质疏松症,对于已出现骨质疏松症的患者根据具体病情选择用双膦酸盐、降钙素、雌激素和甲状旁腺类似物治疗。本文对华法林引发骨质疏松症的发病机制、研究进展和治疗策略进行综述。     

干细胞移植治疗骨质疏松

目前治疗原发性骨质疏松症的药物主要作用于骨形成和骨吸收耦联失调,而对骨髓间充质干细胞(MSCs)与骨质疏松关联的治疗方法尚未研制成功。骨髓间充质干细胞的衰老是原发性骨质疏松症的发病机制之一。间充质干细胞衰老,导致干细胞增殖能力下降,成骨分化能力减弱,成脂分化增强,骨组织成分减少,骨矿物质基质减少,脂肪组织增加,最终导致骨量减少,骨纤维结构异常,进而出现骨质疏松。移植自体、同种异体的MSCs或者基因修饰MSCs可以有效增加局部骨量,提高骨密度,增强骨力学强度,改善局部骨质疏松情况,可纠正骨代谢失衡,减少骨量丢失,增加成骨,有望为治疗骨质疏松提供一种新的策略和方法。     

老年骨质疏松症的药物治疗

据WHO统计,目前骨质疏松症的发病率在常见病、多发病中已跃居第七位,目前我国骨质疏松症患者已达6300万。老年骨质疏松症分为两型,型为绝经后骨质疏松症,型为老年性骨质疏松症。近年临床用于防治骨质疏松症的药物主要有两大类,一类为骨吸收抑制剂,如钙制剂和钙调节剂(雌激...     

Sclerostin与骨质疏松研究进展

骨质疏松症是一种低骨量、骨组织微结构破坏为特征导致骨骼脆性增加和易骨折的全身性疾病,发病率高,给患者带来巨大的身心痛苦,给家庭和社会带来了沉重的经济负担。治疗骨质疏松症最理想的方法是促进成骨（直接增加骨量）,而目前骨质疏松症的治疗大多采用抑制破骨细胞这种间接的方法。SOST／Sclerostin的发现为研究开发促进成骨的药物提供了崭新的思路。本文就Sclerostin与骨质疏松症的研究进展做一综述。     

复合药物治疗绝经后骨质疏松症

应用以雌激素、海螵蛸和维生素Ｄ等为主要成分的复合药物治疗绝经后骨质疏松症１７５例，６个月后随访１５８例，骨痛改善９２．５％，前臂及腰椎骨密度显著提高（Ｐ＜０．０５）；治疗１２个月后随访１２７例，骨痛改善达９６．４％，骨密度进一步提高（Ｐ＜０．０１）。用药初有９．１％的患者出现白带增多或乳房胀不适，几天后症状自行缓解；有３．５％的病人因子宫出血而停药。研究认为复合药物治疗绝经后骨质疏松症具有缓解疼痛，提高骨量，预防骨丢失，副反应轻微的特点。     

骨质疏松症的药物治疗

本文简述了使用骨吸收抑制剂和骨形成刺激剂治疗骨质疏松症的情况，对药物的作用原理、用途、用法和用量、副作用等分别予以介绍。     

Ostéoporose cortisonique: de la physiopathologie au traitement

Corticosteroid-induced osteoporosis, the principal cause of "secondary" osteoporosis, is usually observed in patients under prolonged systemic corticosteroid therapy and results from the multiple effects exerted by these drugs on bone cell metabolism. Corticosteroids reduce the intestinal absorption of calcium and its tubular reabsorption, thereby negativating the calcium balance and inducing a parathyroid reaction. This reaction is responsible for an increase in bone cell remodelling, but the main manifestation of the direct effect of corticosteroids on bone is osteoblast depression, so that there is disparity between bone resorption and formation, which in turn is responsible for bone tissue deficit. Sex hormone deficiency (due to menopause or treatment) and lack of physical activities (due to the causal disease or to iatrogenic myopathy) amplify bone rarefaction. By quantifying the bone loss, modern densitometry methods provide an early risk evaluation. Osteoporosis of varying intensity exposes some 20% of patients to fractures, vertebral collapse and rib fractures. Preventive measures are always recommended, including minimal effective dose corticosteroid therapy, sodium-free diet, calcium and vitamin D supplement, sex hormone replacement and pursuance of physical activities. Once the stage of fractures by osteoporosis has been reached, the "curative" treatment aims at reducing the incidence of new fractures, either by slowing down osteoclast resorption, or by restoring the bone tissue reserve through stimulation of the osteoblasts. The usefulness of these therapeutic measures in the preventive treatment of corticosteroid-induced osteoporosis remains controverted.     

The management of secondary osteoporosis

Secondary osteoporosis is common among patients being evaluated for osteoporosis. All men and premenopausal women with unexplained bone loss or a history of a fragility fracture should undergo a work-up for secondary osteoporosis. Also, postmenopausal women with risk factors for secondary osteoporosis should be carefully evaluated. The evaluation should include a thorough history, physical examination, bone mineral density testing, and laboratory testing. While there is no consensus for a cost-effective laboratory evaluation, some recommendations include: 25-hydroxyvitamin D, parathyroid hormone (PTH), serum and urine calcium, phosphate, creatinine, liver function tests, a complete blood count, testosterone in men, and thyroid-stimulating hormone. After a thorough review of the evaluation for secondary osteoporosis, this chapter reviews the pathophysiology and treatment of secondary osteoporotic disorders, including vitamin D insufficiency, osteomalacia, the osteoporosis of erosive inflammatory arthritis, ankylosing spondylitis, systemic lupus erythematosus, and osteoporosis related to anti-androgenic therapy for prostate cancer and aromatase inhibitor therapy for breast cancer. Physicians have a significant responsibility to evaluate and treat the underlying medical problem that is the cause of secondary osteoporosis and to optimize bone health in the individual patient.     

Basics and management of glucocorticoid-induced osteoporosis

Glucocorticoids interfere with bone metabolism at different levels. Therefore, glucocorticoid-induced osteoporosis (GIO) is the most frequent form of secondary osteoporosis and up to 50 percent of patients on chronic glucocorticoid therapy suffer fractures. This is also because GIO is still under-diagnosed and not adequately treated. Besides, the fracture risk is higher in GIO than in primary osteoporosis even in the presence of equal bone mass density. The risk of osteoporotic fractures increases with dose and duration of glucocorticoid therapy, although the loss of bone mass is more prominent within the first three to twelve months after initiation of treatment. Besides glucocorticoid treatment, other factors, such as e.g. the underlying disease, substantially influence the fracture risk. Therefore, a diagnostic screening is mandatory in each case and should include the patient's history, physical examination, laboratory studies, evaluation of the bone-mass density by dual X-ray absorptiometry and imaging of the spine. Education of the patients and pharmacological prevention are very important, antiresorptive therapy has to be started earlier than in primary osteoporosis and osteoanabolic agents have also been proven to be effective.     

Grundlagen und Management der glukokortikoidinduzierten Osteoporose

Glucocorticoids interfere with bone metabolism at different levels. Therefore, glucocorticoid-induced osteoporosis (GIO) is the most frequent form of secondary osteoporosis and up to 50 percent of patients on chronic glucocorticoid therapy suffer fractures. This is also because GIO is still under-diagnosed and not adequately treated. Besides, the fracture risk is higher in GIO than in primary osteoporosis even in the presence of equal bone mass density. The risk of osteoporotic fractures increases with dose and duration of glucocorticoid therapy, although the loss of bone mass is more prominent within the first three to twelve months after initiation of treatment. Besides glucocorticoid treatment, other factors, such as e.g. the underlying disease, substantially influence the fracture risk. Therefore, a diagnostic screening is mandatory in each case and should include the patient’s history, physical examination, laboratory studies, evaluation of the bone-mass density by dual X-ray absorptiometry and imaging of the spine. Education of the patients and pharmacological prevention are very important, antiresorptive therapy has to be started earlier than in primary osteoporosis and osteoanabolic agents have also been proven to be effective.     

Glucocorticoid-induced osteoporosis: recent findings

The clinical features, pathogenesis and management of bone involvement in Cushing's syndrome are briefly reviewed. Personal data on bone mineral density and markers of bone turnover in Cushing's syndrome and adrenal incidentalomas are also reported. As long ago as 1932, Harvey Cushing recognized osteoporosis as a serious consequence of endogenous hypercortisolism. The introduction of cortisone in the therapy of autoimmune, rheumatic, allergic or dermatologic disorders was followed by several reports of detrimental effects on bone of patients who had undergone prolonged glucocorticoid treatment. Due to the rarity of Cushing's syndrome, most of the studies in the literature on glucocorticoid-induced osteoporosis refer to exogenous over-exposure to cortisone and its synthetic derivatives. Only a small number of works concern endogenous hypercortisolism, even if the characteristics of bone damage seem qualitatively the same. Finally, very few data are reported on the hypothetical detrimental effect on bone in the condition of the silent hypercortisolism of adrenal incidentalomas. Glucocorticoid-induced osteoporosis in Cushing's syndrome often results in vertebral fractures, and bone loss is more evident in trabecular than in cortical bone. Notwithstanding some distinctive features in osteoporosis induced by endogenous and exogenous glucocorticoid excess, the common eventual picture is notable bone damage that involves mainly the trabecular bone. Prompt and effective therapy is mandatory to reduce the risk of fractures. The present options include calcium and vitamin D supplementation, estrogen replacement therapy, bisphosphonates, either oral or parenteral. A novel approach to the clinical problem of glucocorticoid-induced osteoporosis might, in the future, be based on studies on selective glucocorticoid receptor modulators, a new class of synthetic glucocorticoids that exhibit significant anti-inflammatory and immunosuppressive activities, with reduced side effects on bone.     

Steroid induced osteoporosis: prevention and treatment

PURPOSE: Corticosteroid induced osteoporosis (CIO) is the most frequent complication of long-term corticosteroid therapy, and the most frequent cause of secondary osteoporosis. New data from biological, epidemiological and therapeutic studies provide basis for optimal management of this bone disease. MAIN POINTS: Corticosteroids are responsible for both quantitative and qualitative deleterious effects on bone, through their effect on bone cells, mainly on osteoblasts (with both a decrease in osteoblast activity and an increase in apoptosis). Epidemiological studies have shown an increased risk of fractures related to CIO, even for low doses, and during the first 6 months of treatment. Relative risk is 1.3 and 2.6 for peripheral and vertebral fractures respectively. Bone mineral density, measured by dual-energy X-ray absorptiometry, is decreased at spine and hip; the risk of fracture is higher in CIO as compared to post-menopausal osteoporosis, for a similar bone density. Prevention of CIO needs the use of the minimal efficacious dose, and treatment of calcium, vitamin D and gonadal hormones insufficiencies. Patients at risk of fracture, as post-menopausal women with prevalent fractures, should receive a bisphosphonate. PERSPECTIVE: It may be possible to reduce the fracture risk in patients on long-term corticosteroid therapy.     

Osteoporosis associated with rheumatoid arthritis: pathogenesis and management

Rheumatoid arthritis is associated with both localized and generalized osteoporosis. Localized osteoporosis can be considered to be caused by local disease mechanisms, including the generation of factors from activation of the cytokine pathway. The etiology of generalized osteoporosis has been difficult to elucidate, particularly because of the lack of sensitive techniques to measure bone mineral density. The introduction of single- and dual-photon absorptiometry and quantitative computed tomography has allowed more accurate assessment of bone mineral density. In general, bone mineral density loss at appendicular sites does not correlate well with axial bone density loss. Corticosteroid treatment exaggerates the development of osteoporosis in up to 40% of patients with rheumatoid arthritis. Sex hormone status, physical activity, disease duration, and functional class are all significant predictors for the development of osteoporosis. Current therapy for prevention and treatment is based largely on theoretical considerations. Physical activity should be encouraged once acute joint inflammation has settled. Postmenopausal women and amenorrheic premenopausal women will benefit from cyclical estrogen replacement. Patients with low serum 1,25-dihydroxy vitamin D3 levels, and males with low serum testosterone levels, are candidates for replacement therapy with the appropriate hormones. In patients who are receiving corticosteroids the dose should be limited, and oral calcium supplements are of benefit. The use of the newer corticosteroid deflazacort, and disease-modifying immunosuppressive drugs, are discussed. Other therapeutic options which should be considered, although published trials are scarce, are calcitonin and the diphosphonates. Further studies are awaited concerning the optimum prevention and treatment of osteoporosis associated with rheumatoid arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use

All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy. However, there is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive. Teriparatide should be considered as treatment for postmenopausal women and men with severe osteoporosis, as well as for patients with established glucocorticoid-induced osteoporosis who require long-term steroid treatment. Teriparatide should also be considered for the management of individuals at particularly high risk for fractures, including subjects who are younger than age 65 and who have particularly low bone mineral density measurements (T scores < or = 3.5). Teriparatide therapy is not recommended for more than 2 yr, based, in part, on the induction of osteosarcoma in a rat model of carcinogenicity. Total daily calcium intake from both supplements and dietary sources should be limited to 1500 mg together with adequate vitamin D intake (< or =1000 U/d). Monitoring of serum calcium may be safely limited to measurement after 1 month of treatment; mild hypercalcemia may be treated by withdrawing dietary calcium supplements, reducing the dosing frequency of PTH, or both. At present, concurrent therapy with antiresorptive therapy, particularly bisphosphonates, should be avoided, although sequential therapy with such agents may consolidate the beneficial effects upon the skeleton after PTH is discontinued.     

Patterns of medication use before and after bone densitometry: factors associated with appropriate treatment

OBJECTIVE: We examined the medications used by women before and after bone densitometry to determine whether patient or physician factors were associated with appropriate osteoporosis therapy. METHODS: Appropriate osteoporosis treatment was defined as alendronate, etidronate, calcitonin, or hormone replacement therapy (HRT) for women with any bone mineral density (BMD) t score < -2.5 or no osteoporosis therapy, except HRT, for women with t scores > -1.0. We observed a cohort of women who underwent bone densitometry at one outpatient osteoporosis clinic. Medical history, medication use, and demographic data were collected at the time of bone densitometry. A followup questionnaire assessed the medication use patterns since bone densitometry and attitudes about osteoporosis therapy. RESULTS: We recruited 553 women who underwent bone densitometry in 1996. Their mean age was 62 years and 95% were postmenopausal. Prior to bone density scans, 27% of patients used HRT, 15% used bisphosphonates, and 6% used calcitonin. Scan results and surveys revealed that 40% of patients had BMD below a t score of -2.5 at any site. Of women with osteoporosis 78% reported taking an appropriate medication after their scans. Patients most likely to receive appropriate treatment were those who understood their bone densitometry results (odds ratio, OR, 2.5; 95% confidence interval, CI, 1.3 to 4.8) and patients who were taking an osteoporosis medication (OR 1.9; 95% CI 1.0 to 3.6). Neither the specialty of the referring physician nor patients' medical history was associated with use of appropriate osteoporosis therapy. CONCLUSION: Of women with osteoporosis who underwent bone densitometry 78% received appropriate therapy after this test. Patient factors were associated with the likelihood that they received appropriate therapy, suggesting that strategies aimed at educating patients may improve the use of osteoporosis medications.     

Differential therapy of osteoporosis

In the past decade, we observed progress in the differential diagnosis of osteoporosis, mainly because of advanced radiological and laboratory procedures, including new bone markers. Loss of bone can also be related to primary and secondary forms of osteoporosis. Consequently, secondary osteoporosis (and osteomalacia) should be treated primarily according to the original disease. Although etiopathology of primary osteoporosis is still unclean differential therapy should be applied to the different subgroups (juvenile, postmenopausal, and senile osteoporosis). Furthermore, even patients of the same age and sex can be at risk for osteoporosis or have definite osteoporosis. This can be differentiated in "low or high turnover osteoporosis" and should be diagnosed and treated as described. Conjugated estrogens in combination with progesterone decrease the rate of endometrial carcinoma and have been established to be very effective in the treatment of high turnover osteoporosis and patients at high risk of developing manifest osteoporosis. In combination with calcium (1 g/day) total doses of estrogen can be reduced to 0.3 g/day. The same applies for the treatment of low turnover (mostly manifest) osteoporosis with fluoride. Daily doses of fluoride can be decreased from 80 mg sodium fluoride to 50g in combination with calcium. These reductions of daily fluoride doses decreases the rate of side effects and allows longer control periods, provided that bone measurements demonstrate a beneficial long-term effect. The control periods depend on the sensitivity of the bone density measurements. Special indications, modifications, alterations and additions of further drugs are discussed for the individual patient.