Strontium ranelate: a new paradigm in the treatment of osteoporosis

Not one of the currently available medications has, so far, unequivocally demonstrated its ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once osteoporosis is established. Therefore, several new therapies are currently under development to optimize the risk/benefit ratio of osteoporosis treatment. Strontium ranelate is composed of an organic moiety (ranelic acid) and of two atoms of stable nonradioactive strontium. In vitro, strontium ranelate increases collagen and noncollagenic proteins synthesis by mature osteoblast enriched cells. The effects of strontium ranelate on bone formation were confirmed as strontium ranelate enhanced pre-osteoblastic cell replication. The stimulation by strontium ranelate of the replication of osteoprogenitor cell and collagen, as well as noncollagenic protein synthesis in osteoblasts, provides substantial evidence to categorize strontium ranelate as a bone-forming agent. In the isolated rat osteoclast assay, a pre-incubation of bone slices with strontium ranelate induced a dose- dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate also dose-dependently inhibited, in a chicken bone marrow culture, the expression of both carbonic anhydrase II and the alpha-subunit of the vitronectin receptor. These effects showing that strontium ranelate significantly affects bone resorption due to a direct and/or matrix-mediated inhibition of osteoclast activity and also inhibits osteoclasts differentiation, are compatible with the profile of an anti-resorptive drug. In normal rats, administration of strontium ranelate induces an improvement in the mechanical properties of the humerus and/or the lumbar vertebra associated with a commensurate increase in bone dimension, shaft and volume. Strontium ranelate was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomized study. Daily oral dose of 125 mg, 500 mg and 1 g of strontium ranelate were compared with a placebo. At the conclusion of the study, the percent variation of lumbar-adjusted bone mineral density from baseline was significantly different in the group receiving 1 g/day of strontium ranelate compared with placebo (+1.41% vs. -0.98%, respectively). Increase in total hip and neck bone mineral density averages, respectively, 3.2% and 2.5%. Strontium ranelate does not induce any significant adverse reaction compared with those observed in women receiving a placebo for the same duration. In a phase II study, the effect of strontium ranelate in postmenopausal women with vertebral osteoporotic fractures was assessed during a double-blind, placebo-controlled trial. Doses of 500 mg, 1 g and 2 g daily of strontium ranelate or placebo were given to 353 Caucasian women with prevalent osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar-adjusted bone mineral density of the group receiving 2 g of strontium ranelate was + 2.97%. This result was significantly different compared with placebo. A significant increase in bone alkaline phosphatase and, over a 6-month period, a significant decrease in urinary-pyridium crosslinks (NTX) were evidenced. During the second year of treatment, the dose of 2 g was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. Bone histomorphometry showed no mineralization defects. The same percentage of withdrawals following an adverse effect was observed for patients receiving placebo and for those receiving 2 g of strontium ranelate. The compound was further investigated in a large phase III program that included two extensive trials for the treatment of severe osteoporosis, one assessing the effects of strontium ranelate on the risk of vertebral fractures (SOTI) and one evaluating its effects on peripheral (nonspinal) fractures (TROPOS). The primary analysis of the SOTI study, evaluating the effect of 2 g of strontium ranelate on vertebral fracture rates, revealed a 41% reduction in the relative risk of expein the relative risk of experiencing a first new vertebral fracture with strontium ranelate, throughout the 3-year study, compared with placebo. The TROPOS study, showed a significant (p = 0.05) reduction in the relative risk of experiencing a first non-vertebral fracture in the group treated with strontium ranelate throughout the 3-year study compared with placebo in the intention-to-treat population. A 41% reduction in the relative risk of experiencing a hip fracture was demonstrated in the per protocol population. All these results imply that strontium ranelate is a new, effective and safe treatment for vertebral and nonvertebral osteoporosis, with a unique mode of action.     

Strontium ranelate: a new paradigm in the treatment of osteoporosis

In vitro, strontium ranelate increases collagen and non-collagenic protein synthesis by mature osteoblast-enriched cells. The effects of strontium ranelate on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated osteoclast, a preincubation of bone slices with strontium ranelate induced a dose-dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. The drug was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomised study. At the conclusion of the study, the percentage variation of lumbar bone mineral density (BMD) from baseline was significantly different in the group receiving strontium ranelate 1000 mg/day as compared with placebo (+5.53 versus -0.75%, respectively). Increase in total hip and neck BMD averages were 3.2 and 2.5%, respectively. The effect of strontium ranelate in postmenopausal women with established osteoporosis was assessed during a multinational, prospective, double-blind, randomised, placebo-controlled trial. Strontium ranelate (500, 1000, 2000 mg/day) or placebo were given to 353 Caucasian women with prevalent vertebral osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar BMD of the group receiving strontium ranelate 2000 mg was 7.3% (p < 0.001). A significant increase in bone alkaline phophatase (p = 0.002) over a 6-month period and a significant decrease in N-telopeptide crosslinks (p = 0.004) throughout the 2-year period were seen in the group receiving 2000 mg of strontium ranelate. During the second year of treatment, the dose of 2000 mg was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. Bone histomorphometry showed no mineralisation defects. The primary analysis of the SOTI study, evaluating the effect of strontium ranelate 2000 mg on vertebral fracture rates, revealed a 41% reduction in the relative risk of patients experiencing a first new vertebral fracture with strontium ranelate throughout the 3-year study. The TROPOS study showed a significant reduction in the risk of experiencing a first non-vertebral fracture in the group treated with strontium ranelate throughout the 3-year study. A reduction in the risk of experiencing a hip fracture was also demonstrated in the patients treated for ≥ 18 months.     

Strontium ranelate in osteoporosis

Strontium ranelate is composed of an organic moiety (ranelic acid) and of two atoms of stable non-radioactive strontium. In vitro, strontium ranelate increases collagen and non-collagenic proteins synthesis by mature osteoblast enriched cells. The effects of strontium ranelate on bone formation were confirmed as strontium ranelate enhanced pre-osteoblastic cells replication. The stimulation by strontium ranelate of the replication of osteoprogenitor cells and collagen as well as non-collagenic protein synthesis in osteoblasts provides substantial evidence to categorise SR ranelate as a bone forming agent. In the mouse calvaria culture system, SR ranelate induces a dose-dependent inhibition of labelled calcium release. The inhibitory effects of SR ranelate on bone resorption were close to those of salmon calcitonin. In the isolated rat osteoclast assay, a pre-incubation of bone slices with SR ranelate induced a dose-dependent inhibition of the bone resorbing activity of a treated rat osteoclast. SR ranelate also dose-dependently inhibited, in a chicken bone marrow culture, the expression of both CA II and the alpha-subunit of the vitronectin receptor. These effects showing that SR ranelate significantly affects bone resorption due to direct and/or matrix-mediated inhibition of osteoclast activity and also inhibits osteoclasts differentiation are compatible with the profile of an anti-resorptive drug. In normal rats, administration of SR ranelate induces an improvement in the mechanical properties of the humerus and/or the lumbar vertebra associated with a commensurate increase in bone dimension, shaft and volume. This was not related to any change in the stiffness, suggesting the absence of a mineralisation defect. After oral administration of SR ranelate in humans, the absolute bio-availability of SR ranelate is 27 % after a dose of 2g is given as sachets. The simultaneous intake of SR ranelate and calcium remarkably reduces the bio-availability of SR. SR ranelate was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomized study. Daily oral dose of 125 mg, 500 mg, 1 g of SR ranelate were compared to a placebo. At the conclusion of the study, the percent variation of lumbar adjusted BMD from baseline was significantly different in the group receiving 1 g/day of SR as compared to placebo (+ 1.41 % versus 0.98 % respectively). Increase in total hip and neck BMD averages respectively 3.2 % and 2.5 %. SR ranelate does not induce any significant adverse reaction compared to those observed in women receiving a placebo for the same duration. In a phase II study, the effect of SR ranelate in postmenopausal women with vertebral osteoporotic fractures were assessed during a double-blind, placebo-controlled trial. SR ranelate (500 mg, 1 g, 2 g per day) or placebo were given to 353 Caucasian women with prevalent osteoporosis. At the conclusion of this two-year study, the annual increase in lumbar adjusted BMD of the group receiving 2 g of SR ranelate was + 2.97 %. This result was significantly different as compared to placebo. A significant decrease in pyridinium crosslinks (NTX) and an increase in bone specific alkaline phosphatase were evident after 3 and 6 months of treatment. During the second year of treatment, the dose of 2 g was associated with a 4 % reduction in the number of patient experiencing a new vertebral deformity. Bone histomorphometry showed no mineralisation defects. The same percentage of withdrawal following an adverse effect was observed for patients receiving placebo and for those receiving 2 g of strontium ranelate. Currently, strontium ranelate is further investigated in a large Phase III program that includes two extensive trials for the treatment of severe osteoporosis, one assessing SR ranelate effects on the risk of vertebral fractures (SOTI) and one evaluating the effects of SR ranelate on peripheral (non spinal) fractures (TROPOS). The primary analysis of the SOTI study, evaluating the effect of 2 g of strontium ranelate on vertebral fracture rates are expected to be released during the summer 2002.     

Strontium ranelate: a look back at its use for osteoporosis

Importance of the field: Osteoporosis is now considered a major health problem in all developed and in most developing (non-African) countries.

Areas covered in this review: In this review, we provide an extensive literature survey (MEDLINE, PubMed, Cochrane Controlled Register), for articles dealing with osteoporosis management and/or strontium ranelate, from 1920 to 2010.

What the reader will gain : The objective is to provide an extensive, unbiased assessment of the available data allowing strontium ranelate to be placed in perspective with other anti-osteoporosis treatments.

Take home message : Owing to a positive benefit-to-risk ratio, strontium ranelate may now be considered a first-line treatment in the management of osteoporosis.     

雷奈酸锶对大鼠应力缺失性骨丢失的防治作用

摘要： 目的 探讨雷奈酸锶对尾悬吊导致的应力缺失性大鼠骨质疏松的防治效果。方法 6 月龄 SD 大鼠 30 只, 随机均分为 3 组： 正常对照组（A 组）、 尾悬吊组（B 组）、 雷奈酸锶干预组（C 组）。B、 C 两组大鼠采用尾悬吊法制 备应力缺失型骨质疏松大鼠模型, C 组给予 1 g/(kg·d） 雷奈酸锶干预, 4 周后处死所有大鼠, 取左侧股骨检测骨密度, 取左侧胫骨制备非脱钙组织切片并行骨形态计量学检测, 取右侧股骨和胫骨骨髓细胞体外培养并向成骨细胞诱导 分化, 取第 4 代细胞及血清检测骨钙素 （OCN） 的表达。结果 B 组骨密度低于 A 组, C 组高于 B 组 （P＜0.05）。 B 组 骨小梁体积（BV/TV）、 骨小梁数量（Tb.N）、 骨小梁厚度（Tb.Th）低于 A、 C 组, 破骨细胞数（Oc.N）、 骨吸收长度比（Er. Pm）高于 A 组, C 组骨形成率（BFR/BV）、 矿化长度比（L.Pm）高于 B 组, Er.Pm、 Oc.N 低于 B 组（P＜0.05）。B、 C 组 OCN mRNA 表达水平高于 A 组, 但血清中 OCN 水平 B 组低于 A、 C 组 （P＜0.05）。结论 尾悬吊 4 周可造成大鼠骨 丢失, 雷奈酸锶可抑制其骨量丢失, 作用机制可能与其通过上调 OCN 的表达促进骨形成有关。     

A new paradigm in the treatment of osteoporosis: Wnt pathway proteins and their antagonists

The need to develop novel drugs that stimulate bone formation and thereby elevate bone mass (anabolics), as opposed to preventing bone loss (anti-resorptives), has opened new research areas for therapeutic intervention in the treatment of osteoporosis. One of these areas is the Wnt/beta-catenin (canonical) pathway that plays an important role in regulating osteoblast proliferation and differentiation. Alterations in this pathway have been associated with bone disorders characterized by either low or high bone mass. However, as the Wnt/beta-catenin pathway is a ubiquitous mechanism not just exclusively involved in bone formation, targeting Wnts may be a challenge (eg, targeting Wnt activity may induce cancer). Nevertheless, specific pharmacological targets to influence bone formation have been identified in this pathway; these include the Wnt-lipoprotein receptor-related protein 5/6-frizzled complex and Wnt antagonists such as sclerostin. Since sclerostin expression is highly restricted to osteocytes, this specific target may be ideal for anabolic drug therapy.     

Strontium ranelate,a promising disease modifying osteoarthritis drug

Introduction: The articular cartilage and subchondral bone may have potential crosstalk in the development and progression of osteoarthritis (OA). Strontium ranelate (SrR) has the ability to dissociate the bone remodeling process and to change the balance between bone resorption and bone formation. Its effect on subchondral bone makes it a potential disease- modifying osteoarthritis drug (DMOAD) in the treatment of OA. The aim of the current review is to summarize up-to-date pharmacological and clinical data of SrR for OA treatment.

Areas covered: A literature search was performed on PubMed and European Medicines Agency (EMA) website for all publications and documents related to SrR and OA. References of related studies were searched by hand. Treatment with SrR, especially at the dosage of 2 g/day, was associated with reduced radiographic knee OA progression, and with meaningful clinical improvement. It was also significantly associated with decreased MRI-assessed cartilage volume loss (CVL) and bone marrow lesions (BMLs).

Expert opinion: SrR could be a promising DMOAD particularly for OA patients with bone phenotypes. The clinical efficacy and side effects of SrR for OA treatment need to be further investigated in future clinical trials before clinical application.     

Teriparatide (biosynthetic human parathyroid hormone 1-34): a new paradigm in the treatment of osteoporosis

The ideal treatment of osteoporosis should preferably prevent fractures through normalization of bone mass and bone micro-architecture. Biosynthetic human parathyroid hormone 1-34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2-3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 microg/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged.     

Strontium: new drug. Postmenopausal osteoporosis: too many unknowns

(1) Strontium ranelate is marketed in the European Union for the treatment of postmenopausal osteoporosis. Strontium, a cation closely related to calcium, was already used for this purpose in the 1950s but was abandoned because it caused bone mineralization disorders (mainly due to the high doses used at the time). (2) Strontium has only been compared with placebo: there are no clinical trials versus a diphosphonate. (3) On the basis of bone mineral density, two dose-finding studies suggested that, in women who are also taking calcium and vitamin D, the effective minimal dose of strontium is 1 g/day for primary prevention and 2 g/day for secondary prevention. (4) In secondary prevention, a randomised, double-blind trial (SOTI) involving 1649 postmenopausal women who had already had an osteoporotic fracture and were also taking calcium + vitamin D, showed that 2 g strontium daily reduced the risk of symptomatic vertebral fractures compared with placebo (11.3% versus 17.4%) after three years of treatment. (5) Another randomised, double-blind trial (TROPOS) involved 5091 women with osteoporosis of the femur. After three years of treatment with calcium, vitamin D, and either 2 g/day strontium or placebo, the risk of non vertebral osteoporotic fracture was lower in the strontium arm (10.9% versus 9.1%; relative risk 0.85, 95% confidence interval 0.71-1.01), although the difference was only just significant (p = 0.05). This trial failed to show that strontium reduced the risk of femoral fracture. A retrospective subgroup analysis raised the possibility of a preventive effect on hip fracture in patients aged over 74 years, but again the difference had only borderline significance (relative risk 0.64, confidence interval 0.412-0.997). (6) The SOTI and TROPOS studies were subsequently pooled for analysis. A retrospective subgroup analysis of women aged over 80 suggested some efficacy on non vertebral fractures, but this remains to be confirmed in a comparative trial with relevant outcome measures. (7) The reports of these trials include little information on the adverse effects of strontium. Strontium caused a 50% increase in the risk of venous thromboembolism (including pulmonary embolism). Strontium also increased serum creatine kinase activity in 30% of patients. Strontium can affect mental functions, and this effect needs to be quantified. Neurological and muscular adverse effects were inadequately documented, although disorders of this type were observed in animals. (8) The long-term adverse effects of strontium on bone (osteomalacia, pathological fractures, etc.) are unknown. Data from experimental studies and dialysis patients with renal failure raise the possibility of these adverse effects. (9) In practice, there are too many unknowns surrounding the potential risks of strontium while there is not enough evidence of clinical advantages over diphosphonates.     

骨质疏松新药雷奈酸锶研究进展

骨质疏松症是一种以骨量减少,骨组织破坏为特征而导致骨脆性增加并易于骨折的全身性骨骼疾病.本文从作用机制出发,综述首个开发上市的具有抑制破骨细胞吸收和促进骨形成双重作用的新药雷奈酸锶,评价其用于治疗绝经后骨质疏松症的临床安全性和有效性.     

骨质疏松症治疗新选择——唑来膦酸

双膦酸盐是治疗骨质疏松症的一线药物.第3代双膦酸盐--唑来膦酸近年已进入国内临床应用,对治疗妇女绝经后骨质疏松症、糖皮质激素性骨质疏松症以及预防妇女绝经后骨量丢失等有效.然而,仍应高度重视本品可能引起的严重不良事件如下颌骨坏死、急性肾功能衰竭和心律失常等.     

Aromatase inhibitors: a new paradigm in breast cancer treatment

Microsomal cytochrome P450 (CYP 450) enzyme aromatase belongs to CYP 19 super family. It is involved in the conversion of androgens to estrogens. In postmenopausal women the main sites of aromatisation are skin, adipose tissue and breast. Aromatase localized in breast tumor produces sufficient estrogen for its proliferation. Hence it is an important target for the treatment of hormone dependent breast cancer in postmenopausal women. There are mainly two types of aromatase inhibitors, one is steroidal another is nonsteroidal type. The first and second generation aromatase inhibitors encounter the undesirable drug- drug interactions besides being not very specific and plagued with pharmacokinetic problems. Third generation aromatase inhibitors developed recently are more potent and specific with a greater capacity to annihilate circulating estrogen levels. These agents have satisfactory pharmacokinetic profiles and are devoid of major drug-drug interactions. Third generation aromatase inhibitors became drugs of choice for both first and second line treatment of advanced breast cancer. Aromatase inhibitors can also be used for neoadjuvant therapy of breast cancer in which they have achieved better therapeutic efficacy than tamoxifen. Early results of ATAC (Armidex Tamoxifen Alone or Combination) trial suggest that anastrozole is superior to tamoxifen in adjuvant setting for disease free survival, particularly in receptor positive patients, and in reducing the incidence of contralateral breast cancer. Therapeutic potential of aromatase inhibitors stretches beyond the postmenopausal breast cancer treatment as they also play a role in the treatment of estrogen dependent benign and malignant conditions such as gynaecomastia, prostate cancer, fibroadenomata and the induction of ovulation. By virtue of their ability to reduce estrogen levels they pose problems like demineralization of bone, hot flushes and anti-implantation effects.     

Atopic dermatitis: a new treatment paradigm using pimecrolimus

Atopic dermatitis (AD), often called eczema, is a disease characterized by intense pruritus, erythema, dry skin, and inflammation. Pimecrolimus is a novel steroid-free treatment for AD. Consistently positive results have been found with pimecrolimus treatment in infants, children/adolescents, and adults. Its safety record is excellent, and studies have found no clinically relevant drug-related systemic adverse events. In this article, we first review atopic dermatitis and conventional treatment strategies. We then discuss various aspects of pimecrolimus, including pharmacologic properties, toxicology, short- and long-term studies, and safety and adverse events. Finally, we propose a new steroid-sparing treatment strategy for AD.     

治疗绝经后骨质疏松症的新药:abaloparatide

abaloparatide是一种甲状旁腺激素相关蛋白的类似物,2017年4月获美国食品和药物管理局批准用于治疗有高骨折风险的绝经后骨质疏松症。abaloparatide能与甲状旁腺受体1结合,从而起到调节代谢、促进骨骼形成的作用。临床试验证实abaloparatide能够有效降低绝经后骨质疏松症女性患者的新发椎骨和非椎骨骨折的风险,其最常见的不良反应为恶心、头痛、眩晕。     

Ibandronate: new options in the treatment of osteoporosis

Bisphosphonates are currently considered the treatment of choice for corticosteroid-induced male osteoporosis and represent one of the options for the prevention and treatment of postmenopausal osteoporosis. The treatment of osteoporosis with antiresorbing agents requires long-lasting or even lifelong therapies. Oral bisphosphonates are reasonably well tolerated, but a sizable proportion of patients report esophageal symptoms which are occasionally severe. In addition, their intestinal absorption is only 0.5-1% and the presence of any residual food in the stomach completely blocks absorption. Intravenous bisphosphonate administration, which avoids the upper gastrointestinal tolerability concerns associated with oral regimens, may be of considerable value for many patients such as elderly and institutionalized patients because it ensures full treatment compliance, but the intravenous route has to be used with caution since acute renal failure has been observed following the intravenous administration of several bisphosphonates and prolonged intravenous infusions can also be potentially associated with thrombotic complications and infections. Bisphosphonate dosing by intravenous injection could provide a convenient alternative to intravenous infusion that would be suitable for use in the primary care setting and would avoid many of the complications associated with prolonged infusions. This option is viable with the highly potent, nitrogen-containing bisphosphonates such as ibandronate, which, unlike other lower potency bisphosphonates, can be administered as an intravenous injection of only a few milligrams in regimens with extended between-dose intervals. In this review, the data obtained with ibandronate, using both oral administration and intravenous injection, for the treatment and prevention of postmenopausal osteoporosis are summarized.     

雷奈酸锶对抗地塞米松诱导大鼠骨质疏松的作用

目的 研究雷奈酸锶对地塞米松诱导骨质疏松大鼠的作用。方法 30只雌性SD大鼠采用随机数字表法分为5组:空白组,骨质疏松模型组,雷奈酸锶高、中、低剂量组。5周后进行骨形态学及血清指标检测,同时考察不同浓度雷奈酸锶对成骨细胞的体外增殖影响。结果 较模型组(38.00±2.36)μm,雷奈酸锶中、高剂量组的平均骨小梁厚度(48.50±4.05)μm、(52.00±4.44)μm明显升高(P＜0.05),较模型组(189.90±19.27)μm,雷奈酸锶中、高剂量组的骨小梁间距(154.26±13.86)μm、(150.02±20.86)μm明显降低(P＜0.05),表明雷奈酸锶的干预能明显改善骨显微结构指标。雷奈酸锶组高剂量较模型组大鼠血清白介素-6(IL-6)、骨性特异性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRACP-5b)、Ⅰ型胶原C端肽(CTX-I)明显降低(P＜0.05),骨钙素(OCN)、25羟基维生素D(25-HVD)明显升高(P＜0.05)。体外实验表明雷奈酸锶可促进成骨细胞增殖。结论 雷奈酸锶可促进成骨细胞增殖,改善骨形态及多项血清指标,对激素性骨质疏松有一定治疗作用。