Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial

Goldstein, Steven R.; Neven, Patrick; Cummings, Steven R.; Colgan, Terence J.; Runowicz, Carolyn D.; Krpan, Dalibor; Proulx, James; Johnson, Margot; Thompson, David D.; Thompson, John R.; Sriram, Usha

doi:10.1097/gme.0b013e3181e84bb4

Cited by 58 publications

(34 citation statements)

References 15 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, HRTs, as selective estrogen receptor modulators (SERMs), exhibit side effects, and have been associated with an increased risk of coronary heart disease, venous thromboembolic events and exacerbation of menopausal symptoms (13). It has been documented that a consistent number of women taking SERMs exhibit gynecologic symptoms, such as endometrial hyperplasia (14). Therefore, natural alternatives that exert the therapeutic effects of SERMs without the associated side effects are of current interest.…”

Section: Introductionmentioning

confidence: 99%

Psoralen stimulates osteoblast proliferation through the activation of nuclear factor-κB-mitogen-activated protein kinase signaling

Feimeng

Huang³

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Osteoporosis is a systemic skeletal disease that leads to increased bone fragility and susceptibility to fracture. Approximately 50% of postmenopausal women develop osteoporosis as a result of postmenopausal estrogen deficiency. To reduce fractures related to osteoporosis in women, previous studies have focused on therapeutic strategies that aim to increase bone formation or decrease bone resorption. However, pharmacological agents that aim to improve bone fracture susceptibility exhibit side effects. Current studies are investigating natural alternatives that possess the benefits of selective estrogen receptor modulators (SERMs) without the adverse effects. Recent studies have indicated that phytoestrogen may be an ideal natural SERM for the treatment of osteoporosis. In Chinese herbal medicine, psoralen, as the predominant substance of Psoralea corylifolia, is considered to be a phytoestrogen and is used as a remedy for osteoporosis. A number of studies have demonstrated the efficacy of psoralen in bone formation. However, the pathways and underlying molecular mechanisms that participate in psoralen-induced osteoblast formation are not well understood. In the present study, hFOB1.19 cells were treated with psoralen at different concentrations (0, 5, 10, 15 and 20 µM) for 0, 24, 36, 48 and 72 h, respectively. Reverse transcription-quantitative polymerase chain reaction and western blot assays were performed to detect glucose transporter 3 (GLUT3) expression. A cell counting kit-8 assay was used to analyze cell proliferation. In addition the effects of mitogen activated protein kinase inhibitors on extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, p38, p-p38, c-Jun N-terminal kinase (JNK) and p-JNK expressions and cell proliferation were measured, as was the effect of nuclear factor (NF)-κB inhibitor on P65 and GLUT3 expressions and cell proliferation. The results indicated that psoralen stimulates hFOB1.19 cell proliferation in a dose-dependent manner (P<0.05). Phospho-ERK, p38 and JNK were markedly increased by psoralen compared with the control group (P<0.05), and the specific inhibitors of ERK (SCH772984), p38 (SB203580) and JNK (SP600125) reversed the stimulatory effects of psoralen on signal marker phosphorylation (P<0.05). The rate of psoralen-induced cell proliferation was significantly suppressed by inhibitors of ERK, JNK and p38 compared with psoralen treatment alone (P<0.05). In addition, psoralen stimulated osteoblast proliferation via the NF-κB signaling pathway. Therefore, the present findings suggest that psoralen may be a potential natural alternative to SERMs in the treatment of osteoporosis and fractures.

show abstract

Section: Introductionmentioning

confidence: 99%

Psoralen stimulates osteoblast proliferation through the activation of nuclear factor-κB-mitogen-activated protein kinase signaling

Feimeng

Huang³

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Similarly, in the Postmenopausal Evaluation and Risk Reduction with Lasofoxifene study, which was designed to evaluate the effects of lasofoxifene on women with osteoporosis, analysis of vaginal endpoints in a subset of 326 women (abstract data) demonstrated that lasofoxifene significantly improved the maturation index compared with placebo, with benefits sustained for over 3 years (P values not provided) and for vaginal pH (lasofoxifene 0.25 and 0.5 mg/d vs placebo, P = 0.001). 90,91 Two endometrial safety substudies of the Postmenopausal Evaluation and Risk Reduction with Lasofoxifene study have been conducted to establish the incidence of sonographic endometrial effects (N = 326) and other endometrial findings (N = 1,080). 91 At 3 years, lasofoxifene was associated with statistically significant increases from baseline in endometrial thickness (measured by TVU) compared with placebo: least-squares mean change of 1.19 mm (P = 0.001) and 1.43 mm (P = 0.001) for lasofoxifene 0.25 and 0.5 mg/day, respectively.…”

Section: Lasofoxifenementioning

confidence: 99%

“…90,91 Two endometrial safety substudies of the Postmenopausal Evaluation and Risk Reduction with Lasofoxifene study have been conducted to establish the incidence of sonographic endometrial effects (N = 326) and other endometrial findings (N = 1,080). 91 At 3 years, lasofoxifene was associated with statistically significant increases from baseline in endometrial thickness (measured by TVU) compared with placebo: least-squares mean change of 1.19 mm (P = 0.001) and 1.43 mm (P = 0.001) for lasofoxifene 0.25 and 0.5 mg/day, respectively. The absolute incidence rate of endometrial polyps was greater for lasofoxifene than for placebo: 8.8% (P = 0.003) and 5.5% (P = 0.163) for lasofoxifene 0.25 and 0.5 mg/day, respectively (incidence in the placebo group was 3.3%).…”

Section: Lasofoxifenementioning

confidence: 99%

Clinical effects of selective estrogen receptor modulators on vulvar and vaginal atrophy

Pinkerton¹,

Stanczyk

2014

Menopause

View full text Add to dashboard Cite

show abstract

“…Although not determined to be clinically significant, lasofoxifene has been shown to increase endometrial thickness and rates of endometrial polyps and vaginal bleeding [51]. Neither bazedoxifene nor raloxifene have been associated with adverse endometrial effects [52].…”

Section: Safetymentioning

confidence: 99%

“…No endometrial or breast stimulation [46] Lasofoxifene Reduces vertebral and nonvertebral fracture risk [49] Higher incidence of hot flushes and venous thromboembolic events [50] PO administration once daily Some evidence of endometrial effects [51] TSEC Improves BMD and reduces bone turnover in postmenopausal women at increased risk for osteoporosis [59] No breast or endometrial stimulation [60,61] PO administration once daily Rates of adverse events (including cardiovascular and venous thromboembolic events) were similar for TSEC and placebo [60] PO oral, BMD bone mineral density, TSEC tissue selective estrogen complex Convenience SERMs are administered as oral, once daily formulations for the prevention (raloxifene only) and treatment of postmenopausal osteoporosis.…”

Section: Safetymentioning

confidence: 99%

Individualizing osteoporosis therapy

Silverman

Christiansen

2012

Osteoporos Int

View full text Add to dashboard Cite

Guidelines for osteoporosis treatment are available; however, these guidelines suggest when to treat patients, without specific recommendations on what drugs to prescribe in various situations. Choice of osteoporosis therapy should be individualized based on consideration of the efficacy, safety, cost, convenience (i.e., dosing regimen and delivery), and other non-osteoporosis-related benefits associated with each agent. Bisphosphonates, administered orally or intravenously, should be considered first-line therapy, particularly in older patients, owing to their efficacy across multiple skeletal sites; however, there are potential short- and long-term safety concerns. Selective estrogen receptor modulators should be considered for younger postmenopausal women at greater risk for vertebral than hip fractures or as second-line therapy in women who cannot tolerate first-line therapies. Low-dose hormone therapy may be appropriate as prevention in women with menopausal symptoms at lower fracture risk. Calcitonin, with its relatively benign safety profile, may be appropriate for elderly women who may have difficulty following the complex dosing schedules of oral bisphosphonates. Anabolic therapies such as teriparatide should be considered for high-risk patients. Strontium ranelate (approved outside of North America), with both anabolic and antiresorptive properties, may be appropriate for women who cannot tolerate or are unable to take bisphosphonates. Denosumab is a monoclonal antibody appropriate for women at high fracture risk or who have failed other osteoporosis therapies, and may be considered in patients with renal insufficiency. It will be important to incorporate newer agents (e.g., bazedoxifene, tissue selective estrogen complex) into this individualized treatment paradigm to optimize clinical outcomes in patients with osteoporosis.

show abstract

Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial

Abstract: These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women.

Cited by 58 publications

References 15 publications

Psoralen stimulates osteoblast proliferation through the activation of nuclear factor-κB-mitogen-activated protein kinase signaling

Psoralen stimulates osteoblast proliferation through the activation of nuclear factor-κB-mitogen-activated protein kinase signaling

Clinical effects of selective estrogen receptor modulators on vulvar and vaginal atrophy

Individualizing osteoporosis therapy

Contact Info

Product

Resources

About