Background
Tissue | Main effects |
---|---|
Articular cartilage | Reduction of articular cartilage turnover and destruction, regulation of cartilage metabolism, improvement of mechanical properties |
Subchondral bone | Regulation of bone growth and remodeling, promotion of matrix production and mineralization, regulation of osteoblast and osteoclast development and function |
Synovial membrane | Decrease of the proliferation of rheumatoid arthritis-like synovial cells, decrease of proinflammatory cytokine production, reversion of experimental arthritis |
Muscle | Promotion of myoblast proliferation and differentiation, reduction of muscle cell apoptosis, reversion of muscle atrophy and contractile dysfunction |
Estrogen therapy: inconclusive results
Drug name | Type of study | Effects on joint tissues | Reference |
---|---|---|---|
Estradiol | In-vivo OVX + OA rabbits | Cartilage degeneration | [16] |
β-estradiol | In-vivo OVX rabbits | Loss of glycosaminoglycans and collagen | [17] |
17β-estradiol | In-vivo OVX rats | Decrease of CTX-II; prevention of cartilage lesions | [20] |
17β-estradiol | In-vivo postmenopausal OA women | Decrease of 17β-estradiol after menopause | [21] |
Estrogen | In-vivo postmenopausal OA women | Estrogen deficiency may lead to increase of serum IL-6 | [22] |
17β-estradiol | In-vivo murine with knee OA | Inhibition of tibial and patellar subchondral cortical thinning and tibial cartilage damage | [23] |
17β-estradiol | In-vivo OVX + OA mice | Inhibition of bone resorption; decreased ADAMTS-4 and ADAMTS-5 expression | [19] |
β-estradiol | In-vivo OA + OVX murine | Reduction of cartilage and bone turnover | [18] |
β-estradiol | In-vivo OVX + ACLT murine | Regulation of intraarticular neurogenic inflammation | [24] |
17β-estradiol | In-vivo OA + OVX murine | Potentiation of cartilage degradation and subchondral bone erosion and mRNA expression of Fas, FasL, caspase 3, and caspase 8 | [25] |
17β-estradiol | In-vitro rabbit chondrocytes | Upregulation of type II collagen gene | [26] |
17β-estradiol | In-vitro cow mature joint cartilage | Prevention injury-related cell death and GAG release | [27] |
17β-estradiol | In-vitro rabbit chondrocytes | Inhibition of doxorubicin-induced apoptosis | [28] |
17β-estradiol | In-vitro rat OA chondrocytes | Promotion of chondrocyte proliferation | [29] |
Oral estrogen | CSS osteoporotic white women | Reduction of risk of any hip OA | [31] |
HRT | CSS women around menopause | Inverse association of current HRT use and radiological OA of the knee | [35] |
Oral estrogen | CSS women with OA | No positive association of estrogen use with radiographic knee OA | [36] |
ERT | CSS older women | Protection moderately against worsening of radiographic knee OA, but not statistically significant | [37] |
ERT | CSS women | Nonsignificant protective effect for incident knee osteophytes | [38] |
CEE | RCT community-dwelling women | Lower rates of any arthroplasty | [32] |
Estrogen | CSS women | Lower subchondral bone attrition and bone marrow edema-like abnormalities | [33] |
Estrogen | CSS, older women | No significant correlation with knee replacement of OA | [39] |
HT | Prospective study, women around menopause | Correlation highly with the hip or knee replacement rates of OA | [40] |
17β-estradiol | RCT postmenopausal OP women | Decrease of levels of COMP | [34] |
Preclinical studies
Clinical studies
SERM treatment: consistent evidence
Preclinical studies
Drug name | Type of study | Effects on joint tissues | Reference |
---|---|---|---|
Tamoxifen | In-vivo rabbit with OVX + MMX-OA | Reduction of cartilage damage | [48] |
In-vivo rabbit with MMX-OA | Reduction of cartilage damage | [46] | |
In-vivo intact male rabbit with OA | Reduction of cartilage damage | [47] | |
In-vivo rabbit with OVX + MMX-OA | Antagonism of chondrodestructive effects of high-dose estradiol intraarticular administration | [45] | |
CHPPPC | In-vivo Sprague–Dawley rats with OVX | Inhibition of the OVX-induced acceleration of bone and cartilage turnover, and suppression of cartilage damage | [49] |
Levormeloxifene | In-vivo Sprague–Dawley rats with OVX | Prevention of the OVX-induced cartilage and bone changes | [50] |
RCT postmenopausal women | Decrease of CTX-I I by approximately 50 % | [50] | |
Lasofoxifene | In-vivo DBA/1 mice with OVX + arthritis | Reduction of the grade of histologic synovitis and erosions on cartilage and bone | [51] |
Bazedoxifene | In-vivo DBA/1 mice with OVX + arthritis | Reduction of the grade of histologic synovitis and erosions on cartilage and bone | [51] |
In-vivo cynomolgus monkeys with OVX | Inhibition of OVX-induced vertebral deterioration of structural properties | [52] | |
Prospective study in postmenopausal women with type 2 diabetes | Improvement of bone resorption markers | [57] | |
RCT in postmenopausal women with OP | Lowered significantly the cumulative incidences of new vertebral fractures and maintained total hip bone mineral density | [58] | |
Exploratory analysis women with increased fracture risk | Geometry-related improvements in bone strength | [59] | |
RCT in women with menopausal symptoms | Improvement of lumbar spine and total hip BMD | [60] | |
RCT in postmenopausal women with OP | Reduction of the incidences of vertebral and nonvertebral fractures | [61] | |
Raloxifene | In-vitro rat OA-like chondrocytes | Ceases or reduces the matrix degeneration in OA | [53] |
In-vitro human OA-like chondrocytes | Augmented in proteoglycans and a significant decrease of MMP-3 and NO levels | [54] | |
Cross-sectional study in older women with knee OA | Less subchondral bone attrition and bone marrow edema-like abnormalities | [33] | |
RCT in postmenopausal women with back or knee pain | Amelioration of bone and joint pain | [62] | |
Genistein | In-vitro human OA-like chondrocytes | Decrease of NO and IL-1β level in supernatant | [55] |