Search Results (31)

Background: Uterine fibroids (UFs) and endometriosis are gynecological conditions that significantly increase morbidity among women of reproductive age. Relugolix, a novel gonadotropin-releasing hormone receptor antagonist, is approved in combined therapy for the management of symptoms related to these disorders. However, its potential impact on bone mineral density (BMD) and osteoporosis risk should be considered when using a gonadotropin-releasing hormone (GnRH) antagonist. This systematic review aims to evaluate the effects of daily relugolix intake in monotherapy and combination therapy on BMD, ensuring safe long-term management. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed, Medline, and the Cochrane Library. Relevant clinical guidelines from international societies were also reviewed. Studies assessing the impact of relugolix on BMD were selected, and data on treatment efficacy, adverse effects, and bone health outcomes were synthesized. Results: Relugolix monotherapy has been associated with significant BMD loss due to its potent estrogen-suppressing effect. To mitigate this, combination therapy with estradiol and norethisterone acetate has been developed. Although initial monotherapy before transitioning to combination therapy results in transient BMD reduction, clinical trials have demonstrated that relugolix combination therapy maintains BMD over two years while effectively reducing endometriosis- and UF-related symptoms. Conclusions: Relugolix combination therapy is an effective and well-tolerated treatment for UFs and endometriosis, minimizing the risk of hypoestrogenism-related bone loss while maintaining clinical benefits. Although monotherapy may lead to transient BMD reduction, combination therapy appears to stabilize bone health. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at a higher risk of developing bone disorders. Awareness and understanding of the disease are crucial for prevention and early diagnosis. Currently, there is no research on the risk factors and knowledge of bone fragility in the population with IBD in Taiwan. This study aimed to evaluate the risk factors and self-assessed knowledge levels of bone health among patients with IBD in Taiwan. Methods: This single-center cross-sectional study included 59 adult patients. Clinical data, blood tests, bone mineral density (BMD), T-score, Z-score, and questionnaires covering self-assessed knowledge, fracture risks, and physical activity were assessed. The patients were divided into normal and low BMD groups. Results: Of all participants, eighteen (30.5%) had low BMD: six (10.2%) had BMD below the expected range, ten (16.9%) had osteopenia, and two (3.4%) had osteoporosis. Vitamin D insufficiency and deficiency were observed in 26.3% and 66.6% of the patients, respectively. According to multivariate analysis, age and sex hormone deficiency are strongly associated with low BMD. Educational interventions significantly improved the patients’ self-assessed knowledge levels. Conclusions: Age and sex hormone deficiency are significant factors contributing to low BMD in IBD patients. Not only women but also men with IBD who had symptoms of hypogonadism are at high risk for low BMD. Educational interventions improve self-assessment knowledge regarding the relationship between IBD and bone health. Full article

Menopause negatively impacts women’s health. Objectives: The aim of this study was to investigate whether an olive leaf extract (OLE) improves postmenopausal symptoms, body composition, handgrip strength and blood lipid profile in postmenopausal women. In a randomized, double-blinded parallel study design, 60 healthy postmenopausal women aged 47–70 years received either OLE (250 mg/day) or placebo supplementation for 12 weeks. Postmenopausal symptoms were assessed with the Menopause-Specific Quality of Life Questionnaire (MENQoL), the Hot Flash Interference scale (HFI), and body composition and bone mineral density (BMD) with a DXA scan; the lipid profile was measured in the blood serum. After six and twelve weeks of OLE supplementation, the overall MENQoL score significantly improved (estimated mean difference [95% CI]: −0.2 [−0.4−0.2], p = 0.027) compared to the placebo. A significant improvement (+0.017 [0.003, 0.030], p = 0.019) was recorded in the BMD in the right arm in the OLE group compared to the placebo. The intervention did not affect other body composition outcomes. TG concentrations and the TG/HDL-C ratio were significantly decreased (−0.1 [−0.2, 0.0], p = 0.010; −0.1 [−0.2, −0.0], p = 0.029, respectively) in the OLE group compared to the placebo. Twelve weeks of daily OLE supplementation improved postmenopausal symptoms. Further studies are needed to elucidate the mechanisms underlying the observed effects. Full article

Objectives: modulation of gut microbiota by probiotics has been proposed as a target for intervention to reduce bone mineral density (BMD) loss in the postmenopausal period. This study aims to evaluate the effect of Lacticaseibacillus (L.) paracasei LPC100 and Lactiplantibacillus (L.) plantarum LP140 on BMD in postmenopausal women in a multicenter, randomized, double-blind, placebo-controlled trial. Methods: the primary outcome was the change in T-score of the lumbar spine measured by dual-energy X-ray absorptiometry assessed after twelve-month probiotic supplementation. Secondary outcomes included changes in serological markers of inflammation and calcium–phosphate metabolism, body mass index, gastrointestinal symptoms, and satisfaction with the intervention. Results: a decrease in T-score indicating the progressive bone demineralization reached a statistically significant difference in the placebo group (from mean values of 0.06 ± 1.04 to −0.28 ± 1.12, p = 0.041) but not in the probiotic group (0.19 ± 0.99 and −0.08 ± 1.05, respectively, p = 0.125) with a p-value = 0.089 between the groups. No significant differences were found in secondary outcomes with the exception of vitamin D concentration and a significant reduction in some gastrointestinal symptoms in the probiotic group. A significant decrease in vitamin D level was observed only in the placebo group (p = 0.014). Probiotics were safe and well tolerated. Conclusions: this study suggests that the oral administration of L. paracasei LPC100 and L. plantarum LP140 may be a viable strategy to prevent BMD loss and vitamin D deficiency in postmenopausal women, but further research is necessary to confirm clinical benefits and to know the mechanism of action [ClinicalTrial.gov NCT06375668]. Full article

Dystrophin (DMD) gene mutations are associated with skeletal muscle diseases such as Duchenne and Becker Muscular Dystrophy (BMD) and X-linked dilated cardiomyopathy (XL-DCM). To investigate the molecular basis of DCM in a 37-year-old woman. Clinical and genetic investigations were performed. Genetic testing was performed with whole exome sequencing (WES) using the Illumina platform. According to the standard protocol, a variant found by WES was confirmed in all available members of the family by bi-directional capillary Sanger resequencing. The effect of the variant was investigated by using an in silico prediction of pathogenicity. The index case was a 37-year-old woman diagnosed with DCM at the age of 33. A germline heterozygous A>G transversion at nucleotide 10103 in the DMD gene, leading to an aspartic acid–glycine substitution at the amino acid 3368 of the DMD protein (c.10103A>G p.Asp3368Gly), was identified and confirmed by PCR-based Sanger sequencing of the exon 70. In silico prediction suggests that this variant could have a deleterious impact on protein structure and functionality (CADD = 30). The genetic analysis was extended to the first-degree relatives of the proband (mother, father, and sister) and because of the absence of the variant in both parents, the p.Asp3368Gly substitution was considered as occurring de novo. Then, the direct sequencing analysis of her 8-year-old son identified as hemizygous for the same variant. The young patient did not present any signs or symptoms attributable to DCM, but reported asthenia and presented with bilateral calf hypertrophy at clinical examination. Laboratory testing revealed increased levels of creatinine kinase (maximum value of 19,000 IU/L). We report an early presentation of dilated cardiomyopathy in a 33-year-old woman due to a de novo pathogenic variant of the dystrophin (DMD) gene (p.Asp3368Gly). Genetic identification of this variant allowed an early diagnosis of a skeletal muscle disease in her son. Full article

Women going through menopause experience changes in their hormone levels, such as decreased estrogen secretion. Those changes can lead to weight gain and steatosis (fatty liver) due to abnormal lipid metabolism and bone turnover. Natural herbal medicines have been developed to treat and prevent menopausal symptoms. The aim of this study was to evaluate how a mixture of germinated Glycine max (GG) and Angelica gigas Nakai (AG) affected serum lipid profile levels, hepatic damage, inflammation, and bone turnover in ovariectomized (OVX) rats. The animals were randomly allocated into six groups: Sham control group (Sham), OVX control group (OVX), OVX + 50 mg/kg b.w. of GG (GG50) group, and OVX + 25, 50, 100 mg/kg b.w. of GG and AG mixture (GAM; GAM25, GAM50, GAM100) groups. After four weeks of treatment, the GAM groups exhibited decreases in serum lipid profile levels (TC, TG, and Low Density Lipoprotein (LDL)) and increases in High Density Lipoprotein (HDL). Proinflammatory mediators (IL-1β, IL-6, TNF-α, and iNOS) were reduced after the administration of GAM, and the degree of liver damage (ALT, AST) also decreased. Bone resorption (CTX1, NTX1, osteoclasts in H&E staining) decreased in the GAM-treated groups, and bone morphometric markers (BMD, BV/TV, Tb.N) improved compared with the OVX group. Additionally, increased bone formation (ALP, mineralization) and decreased bone resorption (TRACP) were confirmed in in vitro experiments. These results suggest that GAM has anti-obesity and anti-inflammatory effects by preventing dyslipidemia and that it alleviates bone mass loss in OVX rats by inhibiting osteoclastogenesis. Full article

(1) Background: Lumbar spinal stenosis (LSS) causes uncomfortable neuropathic symptoms, which can negatively affect osteoporosis. The aim of this study was to investigate the effect of LSS on bone mineral density (BMD) in patients treated with one of three oral bisphosphonates (ibandronate, alendronate and risedronate) for initially diagnosed osteoporosis. (2) Methods: We included 346 patients treated with oral bisphosphonates for three years. We compared annual BMD T-scores and BMD increases between the two groups according to symptomatic LSS. The therapeutic efficacies of the three oral bisphosphonates in each group were also evaluated. (3) Results: Annual and total increases in BMD were significantly greater in group I (osteoporosis) compared to group II (osteoporosis + LSS). The total increase in BMD for three years was significantly greater in the ibandronate and alendronate subgroups than that in the risedronate subgroup (0.49 vs. 0.45 vs. 0.25, p < 0.001). Ibandronate showed a significantly greater increase in BMD than that of risedronate in group II (0.36 vs. 0.13, p = 0.018). (4) Conclusions: Symptomatic LSS may interfere with the increase in BMD. Ibandronate and alendronate were more effective in treating osteoporosis than risedronate. In particular, ibandronate was more effective than risedronate in patients with both osteoporosis and LSS. Full article

Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD. Full article

Dysferlinopathy covers a spectrum of muscle disorder categorized by two major phenotypes, namely Miyoshi muscular dystrophy type 1 (MMD1, OMIM #254130) and limb-girdle muscular dystrophy autosomal recessive 2 (LGMDR2, OMIM #253601), and two minor symptoms, including asymptomatic hyperCKemia and distal myopathy with anterior tibial onset (DMAT, OMIM #606768). We report the first Korean MMD1 misdiagnosed as Becker muscular dystrophy (BMD), which was caused by a combination of compound heterozygous c.663 + 1G > C and p.Trp992Arg of the DYSF gene. A 70-year-old male previously diagnosed with BMD was admitted for genetic counseling. Since he was clinically suspected to have dysferlinopathy but not BMD, targeted panel sequencing was performed to discover the potential hereditary cause of the suspected muscular dystrophy in the proband. Consequently, two pathogenic single nucleotide variants of the DYSF gene, c.663 + 1G > C (rs398123800) and p.Trp992Arg (rs750028300), associated with dysferlinopathy were identified. These variants were previously reported with variant allele frequencies of 0.000455 (c.663 + 1G > C) and 0.000455 (c.2974T > C; p.Trp992Arg) in the Korean population. This report emphasizes the need for common variant screening in the diagnostic algorithms of certain muscle disorders or gene panels with potential pathogenic effects and high rates of recurrent variants. Full article

Osteoarthritis (OA) is the progressive destruction of articular cartilage with severe symptoms, including pain and stiffness. We investigated the anti-osteoarthritic effects of Prunella vulgaris (PV) and Gentiana lutea (GL) extract in primary cultured chondrocytes RAW 264.7 cells in vitro and destabilization of the medial meniscus (DMM)-induced OA mice in vivo. Primary chondrocytes were induced with IL-1β, and RAW 264.7 cells were treated with LPS and co-incubated with either individual extracts of PV and GL or different ratios of PV and GL mixture. For the OA animal model, the medial meniscus (DMM) was destabilized in 9-week-old male C57BL/6 mice. Treatment of individual PV and GL and combination of PV and GL extracts inhibited the mRNA expression level of COX2 in chondrocytes and RAW 264.7 cells. The optimized inhibitory effect was attained with a PV and GL combination at an 8:2 ratio (PG) without cytotoxic effects. PG extracts prevented the expression of catabolic factors (COX2, Mmp3, Mmp9, and Mmp13) and inflammatory mediator levels (PGE2 and collagenase). In addition, PG decreased subchondral sclerosis and increased BMD in the subchondral region of DMM-induced OA mice with protection of articular cartilage destruction by inhibiting inflammatory processes. This study suggests that PG may be an alternative medicinal herb for treatment of OA. Full article

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare type of premenopausal osteoporosis that occurs mainly in the third trimester or immediately after delivery; one of its most common symptoms is back pain caused by a vertebral fracture. The pathogenesis of PLO is unclear, and there is no accepted consensus regarding the treatment of PLO. Although treatments with drugs such as bisphosphonate, strontium ranelate, denosumab, and teriparatide were reported, there is no report of a patient with PLO treated with romosozumab. We present the first case of a patient with PLO treated with romosozumab following 4-month teriparatide treatment. A 34-year-old primiparous and breastfeeding Japanese woman experienced severe low back pain 1 month postdelivery. She was diagnosed with PLO on the basis of low bone marrow density (BMD) and multiple vertebral fractures with no identified cause of secondary osteoporosis. She was treated with teriparatide injection for 4 months, but the treatment was discontinued because of the patient feeling severe nausea after every teriparatide injection and the appearance of new vertebral fractures. Thereafter, we used romosozumab for 12 months. After the romosozumab treatment, her BMD was increased from the baseline by 23.6% at L1–L4, 6.2% at the femoral neck, and 11.2% at the total hip. Treating PLO with 12-month romosozumab after 4 months of teriparatide injection remarkably increased the BMD of the lumbar spine, femoral neck, and total hip without subsequent fracture. Romosozumab has potential as a therapeutic option to improve the BMD and reduce the subsequent fracture risk of patients with PLO. Full article

Menopausal hormone deficiency can exert multiple effects on various organs. Vulvovaginal atrophy (VVA) is among the most widespread and disabling post-menopausal disorder. Hormonal changes can also result in a markedly increased rate of bone mineral density (BMD) loss. Ospemifene (OSP) is an SERM indicated to treat vulvar and vaginal atrophy (VVA) in postmenopausal women. This study evaluates the long-term effects of ospemifene therapy on bone metabolism and bone mineral parameters in postmenopausal women reporting VVA/GSM. Methods: Women reporting VVA symptoms were included. Bone health profile was investigated in 61 subjects treated with OSP (OSPG) (60 mg/day) and compared with a control group (CG) (n = 67) over 12 months. Results: In the CG, BMD and T-score statistically decreased at the femoral neck (FN), total femur (TF), and lumbar spine (L1–L4). In the OSPG, BMD decreased significantly at FN but tended to remain stable at TF and L1–L4. No changes were observed in bone mineral markers after one year in either group, except BAP, which decreased in OSPG. Conclusions: Long-term OSP treatment improves bone mineral markers at TF and LS and slows bone loss at FN compared to the control group. Overall, OSP exerts a protective effect on bone loss in healthy menopausal women with VVA. Full article

Background: To explore motives for combat sport participation, weight regulation practices, symptoms of low energy availability (LEA), disordered eating (DE) or eating disorders (ED), and any experiences with sexual harassment (SH) among female combat-sport athletes. Methods: In total, 29 athletes were recruited by social media and in clubs. Participants responded to a questionnaire on health behavior and mental health and completed diet registration and a DXA-scan. Results: Most athletes started combat sports to feel empowered and experienced an inclusive milieu, but the frequency of health issues was high. A total of 21–67% had symptoms of ED, suffered from injuries, had low site-specific BMD, and/or symptoms of LEA. Athletes had insufficient intake of energy and nutrients, and <50% received any dietary information or guidance from their clubs. Most athletes complied with favorable weight-loss strategies; still, >20% used unfavorable methods and rapid weight-loss periods. A total of 70% of the athletes had experienced SH, of which 41% experienced SH within the combat-sport context. Conclusion: Combat sport offers an inclusive milieu, which may increase women’s health and confidence; still, our results indicates a need for actions to safeguard female combat-sport athletes’ mental and physical health, implying a cultural change within the community of combat sport and a need for increased health and nutrition literacy. Full article

(1) Background: The aim of the present pilot study was to study the effect of a new oral gonadotropin-releasing hormone antagonist on adenomyosis. (2) Methods: Eight premenopausal women, aged between 37 and 45 years, presenting with heavy menstrual bleeding, pelvic pain, and dysmenorrhea due to diffuse and disseminated uterine adenomyosis, confirmed by magnetic resonance imaging (MRI), received 200 mg linzagolix once daily for a period of 12 weeks, after which they were switched to 100 mg linzagolix once daily for another 12 weeks. The primary efficacy endpoint was the change in volume of the adenomyotic uterus from baseline to 24 weeks, evaluated by MRI. Secondary efficacy endpoints included the change in uterine volume from baseline to 12 and 36 weeks by MRI, and also weeks 12, 24, and 36 assessed by transvaginal ultrasound (TVUS). Other endpoints were overall pelvic pain, dysmenorrhea, non-menstrual pelvic pain, dyspareunia, amenorrhea, quality of life measures, bone mineral density (BMD), junctional zone thickness, and serum estradiol values. (3) Results: Median serum estradiol was suppressed below 20 pg/mL during the 12 weeks on linzagolix 200 mg, and maintained below 60 pg/mL during the second 12 weeks on linzagolix 100 mg. At baseline, the mean ± SD uterine volume was 333 ± 250 cm³. After 24 weeks of treatment, it was 204 ± 126 cm³, a reduction of 32% (p = 0.0057). After 12 weeks, the mean uterine volume was 159 ± 95 cm³, a reduction of 55% from baseline (p = 0.0001). A similar pattern was observed when uterine volume was assessed by TVUS. Improvements in overall pelvic pain, dysmenorrhea, non-menstrual pelvic pain, dyspareunia, and dyschezia, as well as quality of life measured using the EHP-30 were also observed. Mean percentage BMD loss at 24 weeks was, respectively, −2.4%, −1.3%, and −4.1% for the spine, femoral neck, and total hip. The most common adverse events were hot flushes, which occurred in 6/8 women during the first 12 weeks, and 1/8 women between 12 and 24 weeks. (4) Conclusions: Linzagolix at a dose of 200 mg/day reduced uterine volume, and improved clinically relevant symptoms. Treatment with 100 mg thereafter retains the therapeutic benefits of the starting dose while minimizing side effects. This ‘hit hard first and then maintain’ approach may be the optimal way to treat women with symptomatic adenomyosis. Full article

Adequate serum vitamin D and iron levels are thought to influence physical training adaptations and mood positively. The primary purpose of this prospective, observational study was to investigate relationships between serum 25-OH vitamin D/25(OH)D and serum ferritin levels with body composition and athlete burnout symptoms. Seventy-three collegiate athletes (female: n = 49; male: n = 24) from indoor (swimming, basketball) and outdoor (soccer, cross-country) sports were tested pre-season and post-season for serum 25(OH)D and serum ferritin (nutrient biomarkers) via venipuncture; body composition (total lean mass, bone mineral density/BMD, and % body fat) via dual energy X-ray absorptiometry (DXA) scans; and athlete burnout symptoms (post-season) via the athlete burnout questionnaire (ABQ). When male and female cohorts were combined, significant correlations (Pearson’s r) were noted between pre-season serum 25(OH)D versus the change (∆: post-season minus pre-season) in both BMD (r = −0.34; p = 0.0003) and % body fat (r = −0.28; p = 0.015). Serum ferritin ∆ was significantly associated with lean mass ∆ (r = −0.34; p = 0.003). For burnout symptoms, serum 25(OH)D ∆ significantly explained 20.6% of the variance for devaluation of the sport in the male cohort only. Across time, serum 25(OH)D levels decreased while serum ferritin levels increased, non-significantly, in both males and females. Relationships between nutrient biomarkers and body composition were opposite of physiological expectations. Full article