Pub Date : 2024-05-30eCollection Date: 2024-07-01DOI: 10.1093/jbmrpl/ziae073
Sungjae Shin, Namki Hong, Yumie Rhee
Raloxifene increases lumbar spine bone mineral density (BMD) and lowers vertebral fracture risk in patients with osteoporosis. However, few prospective clinical trials have studied its efficacy in postmenopausal women with osteopenia. This study investigated the efficacy of raloxifene in postmenopausal women with osteopenia. An investigator-initiated, randomized, open-label, prospective, single-center trial was conducted in 112 postmenopausal women with osteopenia. Osteopenia was defined based on the lowest BMD T-score in the lumbar spine, femoral neck, or total hip (-2.5 < lowest T-score < -1.0). Participants were randomly assigned to receive raloxifene 60 mg/day plus cholecalciferol 800 IU/day (RalD) or cholecalciferol 800 IU/day (VitD) for 48 wk. At baseline, mean age (63.1 ± 6.8 yr) did not differ between the two groups. However, in the RalD group, mean body mass index (BMI) and baseline T-score were lower, while 25-hydroxyvitamin D level was higher. At 48 wk, the RalD group showed a greater increase in lumbar spine BMD (RalD vs. VitD; 2.6% vs. -0.6%, P =.005) and attenuated the total hip BMD loss (-0.3% vs. -2.9%, P = .003). The effect of raloxifene on the lumbar spine remained significant after adjustment for age, BMI, baseline BMD T-score, and other covariates (adjusted β: +3.05 vs. VitD, P =.015). In subgroup analysis, the difference in lumbar spine BMD between the RalD and VitD groups was robust in those with severe osteopenia group (lowest T-score ≤ -2.0). Raloxifene plus cholecalciferol significantly improved lumbar spine BMD and attenuated total hip BMD loss compared with cholecalciferol alone, with a more robust effect in severe osteopenia. Clinical trial registration: The trial was registered with ClinicalTrials.gov (NCT05386784).
雷洛昔芬可增加骨质疏松症患者腰椎骨矿物质密度（BMD），降低脊椎骨折风险。然而，很少有前瞻性临床试验研究其对绝经后骨质疏松症女性的疗效。本研究调查了雷洛昔芬对绝经后骨质疏松症妇女的疗效。研究人员对 112 名绝经后骨质疏松症妇女进行了一项随机、开放标签、前瞻性、单中心试验。骨质疏松症是根据腰椎、股骨颈或全髋骨最低 BMD T 评分（-2.5，P =.005）来定义的，并可减轻全髋骨 BMD 损失（-0.3% 对 -2.9%，P = .003）。调整年龄、体重指数、基线 BMD T 评分和其他协变量后，雷洛昔芬对腰椎的影响仍然显著（调整后 β：+3.05 vs. VitD，P =.015）。在亚组分析中，RalD 组与 VitD 组之间腰椎 BMD 的差异在严重骨质疏松症组（最低 T 评分≤-2.0）中表现明显。与单用胆钙化醇相比，雷洛昔芬加胆钙化醇能明显改善腰椎BMD，减轻髋关节BMD的总损失，对严重骨质疏松症患者的效果更显著。临床试验注册：该试验已在 ClinicalTrials.gov 注册（NCT05386784）。
{"title":"A randomized controlled trial of the effect of raloxifene plus cholecalciferol versus cholecalciferol alone on bone mineral density in postmenopausal women with osteopenia.","authors":"Sungjae Shin, Namki Hong, Yumie Rhee","doi":"10.1093/jbmrpl/ziae073","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae073","url":null,"abstract":"<p><p>Raloxifene increases lumbar spine bone mineral density (BMD) and lowers vertebral fracture risk in patients with osteoporosis. However, few prospective clinical trials have studied its efficacy in postmenopausal women with osteopenia. This study investigated the efficacy of raloxifene in postmenopausal women with osteopenia. An investigator-initiated, randomized, open-label, prospective, single-center trial was conducted in 112 postmenopausal women with osteopenia. Osteopenia was defined based on the lowest BMD T-score in the lumbar spine, femoral neck, or total hip (-2.5 < lowest T-score < -1.0). Participants were randomly assigned to receive raloxifene 60 mg/day plus cholecalciferol 800 IU/day (RalD) or cholecalciferol 800 IU/day (VitD) for 48 wk. At baseline, mean age (63.1 ± 6.8 yr) did not differ between the two groups. However, in the RalD group, mean body mass index (BMI) and baseline T-score were lower, while 25-hydroxyvitamin D level was higher. At 48 wk, the RalD group showed a greater increase in lumbar spine BMD (RalD vs. VitD; 2.6% vs. -0.6%, <i>P</i> =.005) and attenuated the total hip BMD loss (-0.3% vs. -2.9%, <i>P</i> = .003). The effect of raloxifene on the lumbar spine remained significant after adjustment for age, BMI, baseline BMD T-score, and other covariates (adjusted β: +3.05 vs. VitD, <i>P</i> =.015). In subgroup analysis, the difference in lumbar spine BMD between the RalD and VitD groups was robust in those with severe osteopenia group (lowest T-score ≤ -2.0). Raloxifene plus cholecalciferol significantly improved lumbar spine BMD and attenuated total hip BMD loss compared with cholecalciferol alone, with a more robust effect in severe osteopenia. <i>Clinical trial registration</i>: The trial was registered with ClinicalTrials.gov (NCT05386784).</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roberta Zerlotin, Angela Oranger, Patrizia Pignataro, Manuela Dicarlo, Lorenzo Sanesi, Clelia Suriano, Giuseppina Storlino, Rita Rizzi, Anna Mestice, Sante Di Gioia, Giorgio Mori, Maria Grano, Graziana Colaianni, Silvia Colucci
Bone disease (BD) associated with multiple myeloma (MM) is characterized by osteolytic lesions and pathological fractures, which remain a therapeutic priority despite new drugs improving MM patient survival. Antiresorptive molecules represent the main option for the treatment of MMBD whereas osteoanabolic molecules are under investigation. Among these latter, we here focused on the myokine irisin, able to enhance bone mass in healthy mice, prevent bone loss in osteoporotic mouse models, and accelerate fracture healing in mice. Therefore, we investigated irisin effect on MMBD in a mouse model of MM induced by intratibial injection of myeloma cells followed by weekly administration of 100 μg/Kg of recombinant-irisin for 5 weeks. By micro-Ct analysis, we demonstrated that irisin improves MM-induced trabecular bone damage by partially preventing the reduction of femur Trabecular Bone Volume/Total Volume (p = 0.0028), Trabecular Number (p = 0.0076), and Trabecular Fractal Dimension (p = 0.0044), and increasing Trabecular Separation (p = 0.0003) in MM mice. In cortical bone, irisin downregulates the expression of Sclerostin, the bone formation inhibitor, and RankL, the pro-osteoclastogenic molecule, and in bone marrow (BM) upregulates Opg, the anti-osteoclastogenic cytokine. We found that in the BM tibia of irisin-treated MM mice, the percentage of MM cells displays a reduction trend, while in the femur it decreases significantly. This is in line with the in vitro reduction of myeloma cell viability after 48 hours of irisin stimulation at both 200 and 500 ng/ml and after 72 hours already at 100 ng/ml rec-irisin. These results could be due to irisin ability to downregulate the expression of Notch 3, important for cell-to-cell communication in the tumor niche, and Cyclin D1, regulator of cell cycle progression, supporting an inhibitory effect of irisin in MM cell proliferation. Overall, our findings suggest that irisin could be a new promising strategy to counteract MMBD and tumor burden in one shot.
与多发性骨髓瘤（MM）相关的骨病（BD）以溶骨性病变和病理性骨折为特征，尽管新药提高了 MM 患者的生存率，但这仍然是治疗的重点。抗骨吸收分子是治疗多发性骨髓瘤相关性骨病的主要选择，而骨合成代谢分子正在研究之中。在后者中，我们重点研究了肌动蛋白鸢尾素，它能够增强健康小鼠的骨量，防止骨质疏松小鼠模型中的骨丢失，并加速小鼠骨折愈合。因此，我们在骨髓瘤小鼠模型中研究了鸢尾素对MMBD的影响，该模型是通过胫骨内注射骨髓瘤细胞诱导的，随后每周注射100微克/千克重组鸢尾素，共注射5周。通过显微 CT 分析，我们发现鸢尾素能部分防止 MM 小鼠股骨骨小梁体积/总体积（p = 0.0028）、骨小梁数量（p = 0.0076）和骨小梁分形尺寸（p = 0.0044）的减少，并增加骨小梁分离度（p = 0.0003），从而改善 MM 诱导的骨小梁损伤。在皮质骨中，鸢尾素会下调骨形成抑制因子 Sclerostin 和促破骨细胞生成分子 RankL 的表达，而在骨髓（BM）中则会上调抗破骨细胞生成细胞因子 Opg 的表达。我们发现，在鸢尾素处理过的 MM 小鼠的骨髓胫骨中，MM 细胞的百分比呈下降趋势，而在股骨中则显著下降。这与体外骨髓瘤细胞存活率在鸢尾素（200 和 500 纳克/毫升）刺激 48 小时后降低以及在 100 纳克/毫升 rec-irisin 刺激 72 小时后降低的情况一致。这些结果可能是由于鸢尾素能够下调对肿瘤龛中细胞间通讯非常重要的 Notch 3 和细胞周期进展调节因子 Cyclin D1 的表达，从而支持了鸢尾素对 MM 细胞增殖的抑制作用。总之，我们的研究结果表明，鸢尾素可能是一种一次性对抗MMBD和肿瘤负荷的有前途的新策略。
{"title":"Irisin prevents trabecular bone damage and tumor invasion in a mouse model of multiple myeloma","authors":"Roberta Zerlotin, Angela Oranger, Patrizia Pignataro, Manuela Dicarlo, Lorenzo Sanesi, Clelia Suriano, Giuseppina Storlino, Rita Rizzi, Anna Mestice, Sante Di Gioia, Giorgio Mori, Maria Grano, Graziana Colaianni, Silvia Colucci","doi":"10.1093/jbmrpl/ziae066","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae066","url":null,"abstract":"\u0000 Bone disease (BD) associated with multiple myeloma (MM) is characterized by osteolytic lesions and pathological fractures, which remain a therapeutic priority despite new drugs improving MM patient survival. Antiresorptive molecules represent the main option for the treatment of MMBD whereas osteoanabolic molecules are under investigation. Among these latter, we here focused on the myokine irisin, able to enhance bone mass in healthy mice, prevent bone loss in osteoporotic mouse models, and accelerate fracture healing in mice. Therefore, we investigated irisin effect on MMBD in a mouse model of MM induced by intratibial injection of myeloma cells followed by weekly administration of 100 μg/Kg of recombinant-irisin for 5 weeks. By micro-Ct analysis, we demonstrated that irisin improves MM-induced trabecular bone damage by partially preventing the reduction of femur Trabecular Bone Volume/Total Volume (p = 0.0028), Trabecular Number (p = 0.0076), and Trabecular Fractal Dimension (p = 0.0044), and increasing Trabecular Separation (p = 0.0003) in MM mice. In cortical bone, irisin downregulates the expression of Sclerostin, the bone formation inhibitor, and RankL, the pro-osteoclastogenic molecule, and in bone marrow (BM) upregulates Opg, the anti-osteoclastogenic cytokine. We found that in the BM tibia of irisin-treated MM mice, the percentage of MM cells displays a reduction trend, while in the femur it decreases significantly. This is in line with the in vitro reduction of myeloma cell viability after 48 hours of irisin stimulation at both 200 and 500 ng/ml and after 72 hours already at 100 ng/ml rec-irisin. These results could be due to irisin ability to downregulate the expression of Notch 3, important for cell-to-cell communication in the tumor niche, and Cyclin D1, regulator of cell cycle progression, supporting an inhibitory effect of irisin in MM cell proliferation. Overall, our findings suggest that irisin could be a new promising strategy to counteract MMBD and tumor burden in one shot.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141103423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Kooblall, M. Stevenson, R. Heilig, Michelle Stewart, Ben Wright, Helen Lockstone, David Buck, Roman Fischer, Sara Wells, K. Lines, L. Teboul, Raoul C. Hennekam, Rajesh V Thakker
Nuclear factor I/X (NFIX) mutations are associated with two skeletal dysplasias, Marshall-Smith (MSS) and Malan (MAL) syndromes. NFIX encodes a transcription factor that regulates expression of genes, including Bobby sox (BBX) and glial fibrillary acidic protein (GFAP) in neural progenitor cells and astrocytes, respectively. To elucidate the role of NFIX mutations in MSS, we studied their effects in fibroblast cell lines obtained from 5 MSS unrelated patients and 3 unaffected individuals. The 5 MSS NFIX frameshift mutations in exons 6-8 comprised 3 deletions (c.819-732_1079-948del, c. 819-471_1079-687del, c.819-592_1079-808del), an insertion (c. 1037_1038insT) and a duplication (c.1090dupG). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses using MSS and unrelated control fibroblasts and in vitro expression studies in monkey kidney fibroblast (COS-7) cells showed that frameshift mutations in NFIX exons 6-8 generated mutant transcripts that were not cleared by nonsense-mediated-decay mechanisms and encoded truncated NFIX proteins. Moreover, BBX or GFAP expression were unaffected in the majority of MSS fibroblasts. To identify novel NFIX downstream target genes, RNA sequencing and proteomics analyses were performed on mouse embryonic fibroblast (MEF) cells derived from control Nfix+/+, Nfix+/Del2, Nfix+/Del24, NfixDel24/Del24, Nfix+/Del140 and NfixDel140/Del140 mice, compared to NfixDel2/Del2 mice which had developmental, skeletal and neural abnormalities. This identified 191 transcripts and 815 proteins misregulated in NfixDel2/Del2 MEFs with ≥2-fold-change (p < 0.05). Validation studies using qRT-PCR and Western blot analyses confirmed that two genes, cellular retinoic acid binding protein 2 (Crabp2) and vascular cell adhesion molecule 1 (Vcam1), were misregulated at the RNA and protein levels in NfixDel2/Del2 MEFs, and that CRABP2 and VCAM1 expression were altered in 60-100% of MSS fibroblast cells. Furthermore, in vitro luciferase reporter assays confirmed that NFIX directly regulates CRABP2 promoter activity. Thus, these altered genes and pathways may represent possible targets for drugs as potential treatments and therapies for MSS.
{"title":"Identification of cellular retinoic acid binding protein 2 (CRABP2) as downstream target of nuclear factor 1/X (NFIX): implications for skeletal dysplasia syndromes","authors":"K. Kooblall, M. Stevenson, R. Heilig, Michelle Stewart, Ben Wright, Helen Lockstone, David Buck, Roman Fischer, Sara Wells, K. Lines, L. Teboul, Raoul C. Hennekam, Rajesh V Thakker","doi":"10.1093/jbmrpl/ziae060","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae060","url":null,"abstract":"\u0000 Nuclear factor I/X (NFIX) mutations are associated with two skeletal dysplasias, Marshall-Smith (MSS) and Malan (MAL) syndromes. NFIX encodes a transcription factor that regulates expression of genes, including Bobby sox (BBX) and glial fibrillary acidic protein (GFAP) in neural progenitor cells and astrocytes, respectively. To elucidate the role of NFIX mutations in MSS, we studied their effects in fibroblast cell lines obtained from 5 MSS unrelated patients and 3 unaffected individuals. The 5 MSS NFIX frameshift mutations in exons 6-8 comprised 3 deletions (c.819-732_1079-948del, c. 819-471_1079-687del, c.819-592_1079-808del), an insertion (c. 1037_1038insT) and a duplication (c.1090dupG). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses using MSS and unrelated control fibroblasts and in vitro expression studies in monkey kidney fibroblast (COS-7) cells showed that frameshift mutations in NFIX exons 6-8 generated mutant transcripts that were not cleared by nonsense-mediated-decay mechanisms and encoded truncated NFIX proteins. Moreover, BBX or GFAP expression were unaffected in the majority of MSS fibroblasts. To identify novel NFIX downstream target genes, RNA sequencing and proteomics analyses were performed on mouse embryonic fibroblast (MEF) cells derived from control Nfix+/+, Nfix+/Del2, Nfix+/Del24, NfixDel24/Del24, Nfix+/Del140 and NfixDel140/Del140 mice, compared to NfixDel2/Del2 mice which had developmental, skeletal and neural abnormalities. This identified 191 transcripts and 815 proteins misregulated in NfixDel2/Del2 MEFs with ≥2-fold-change (p < 0.05). Validation studies using qRT-PCR and Western blot analyses confirmed that two genes, cellular retinoic acid binding protein 2 (Crabp2) and vascular cell adhesion molecule 1 (Vcam1), were misregulated at the RNA and protein levels in NfixDel2/Del2 MEFs, and that CRABP2 and VCAM1 expression were altered in 60-100% of MSS fibroblast cells. Furthermore, in vitro luciferase reporter assays confirmed that NFIX directly regulates CRABP2 promoter activity. Thus, these altered genes and pathways may represent possible targets for drugs as potential treatments and therapies for MSS.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140976355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iron is a vital trace element and exerts opposing effects on bone in both iron overload and iron deficiency situations. Remarkably, iron supplementation through intravenous infusion in patients with iron deficiency can also have detrimental effects on bone in special cases. The diverse mechanisms underlying these effects and their manifestations contribute to the complexity of this relationship. Iron overload impacts both bone resorption and formation, accelerating bone resorption while reducing bone formation. These effects primarily result from the direct action of reactive oxygen species (ROS), which influence the proliferation, differentiation, and activity of both osteoclasts and osteoblasts differently. This imbalance favors osteoclasts and inhibits the osteoblasts. Simultaneously, multiple pathways, including bone morphogenic proteins, RANK ligand, and others, contribute to these actions, leading to a reduction in bone mass and an increased susceptibility to fractures. In contrast, iron deficiency induces low bone turnover due to energy and co-factor deficiency, both of which require iron. Anemia increases the risk of fractures in both men and women. This effect occurs at various levels, reducing muscular performance and, on the bone-specific level, decreasing bone mineral density. Crucially, anemia increases the synthesis of the phosphaturic hormone iFGF23, which is subsequently inactivated by cleavage under physiological conditions. Thus, iFGF23 levels and phosphate excretion are not increased. However, in specific cases where anemia has to be managed with intravenous iron treatment, constituents — particularly maltoses — of the iron infusion suppress the cleavage of iFGF23. As a result, patients can experience severe phosphate wasting and, consequently, hypophosphatemic osteomalacia. This condition is often overlooked in clinical practice and is often caused by ferric carboxymaltose. Ending iron infusions or changing the agent, along with phosphate and vitamin D supplementation, can be effective in addressing this issue.
{"title":"Iron and bones: Effects of iron overload, deficiency and anemia treatments on bone","authors":"Felix N von Brackel, Ralf Oheim","doi":"10.1093/jbmrpl/ziae064","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae064","url":null,"abstract":"\u0000 Iron is a vital trace element and exerts opposing effects on bone in both iron overload and iron deficiency situations. Remarkably, iron supplementation through intravenous infusion in patients with iron deficiency can also have detrimental effects on bone in special cases. The diverse mechanisms underlying these effects and their manifestations contribute to the complexity of this relationship. Iron overload impacts both bone resorption and formation, accelerating bone resorption while reducing bone formation. These effects primarily result from the direct action of reactive oxygen species (ROS), which influence the proliferation, differentiation, and activity of both osteoclasts and osteoblasts differently. This imbalance favors osteoclasts and inhibits the osteoblasts. Simultaneously, multiple pathways, including bone morphogenic proteins, RANK ligand, and others, contribute to these actions, leading to a reduction in bone mass and an increased susceptibility to fractures. In contrast, iron deficiency induces low bone turnover due to energy and co-factor deficiency, both of which require iron. Anemia increases the risk of fractures in both men and women. This effect occurs at various levels, reducing muscular performance and, on the bone-specific level, decreasing bone mineral density. Crucially, anemia increases the synthesis of the phosphaturic hormone iFGF23, which is subsequently inactivated by cleavage under physiological conditions. Thus, iFGF23 levels and phosphate excretion are not increased. However, in specific cases where anemia has to be managed with intravenous iron treatment, constituents — particularly maltoses — of the iron infusion suppress the cleavage of iFGF23. As a result, patients can experience severe phosphate wasting and, consequently, hypophosphatemic osteomalacia. This condition is often overlooked in clinical practice and is often caused by ferric carboxymaltose. Ending iron infusions or changing the agent, along with phosphate and vitamin D supplementation, can be effective in addressing this issue.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140980733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brandon R. Grossardt, Hilal Maradit Kremers, Adam R Miller, Bertram L. Kasiske, Arthur J Matas, Sundeep Khosla, Walter K. Kremers, Hatem Amer, Rajiv Kumar
In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3 months and 36 months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared to matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products (AGEs) in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89 pg/mL vs. controls 38.79 pg/mL, percent difference = -12.6%; P < 0.001), increases in both parathyroid hormone (PTH when corrected for ionized calcium; donors mean 52.98 pg/mL vs. controls 46.89 pg/mL,% difference 13%; P = 0.03) and ionized calcium levels (donors mean 5.13 mg/dL vs. controls 5.04 mg/dL; P < 0.001) and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency towards thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.
{"title":"Persistent changes in calcium-regulating hormones and bone turnover markers in living kidney donors more than 20 years after donation","authors":"Brandon R. Grossardt, Hilal Maradit Kremers, Adam R Miller, Bertram L. Kasiske, Arthur J Matas, Sundeep Khosla, Walter K. Kremers, Hatem Amer, Rajiv Kumar","doi":"10.1093/jbmrpl/ziae067","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae067","url":null,"abstract":"\u0000 In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3 months and 36 months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared to matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products (AGEs) in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89 pg/mL vs. controls 38.79 pg/mL, percent difference = -12.6%; P < 0.001), increases in both parathyroid hormone (PTH when corrected for ionized calcium; donors mean 52.98 pg/mL vs. controls 46.89 pg/mL,% difference 13%; P = 0.03) and ionized calcium levels (donors mean 5.13 mg/dL vs. controls 5.04 mg/dL; P < 0.001) and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency towards thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140982050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Dahir, Steven W Ing, Chad Deal, Andrew Messali, Toby Bates, E. Rush
Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. This study assessed the impact of treatment with asfotase alfa on patient-reported outcomes (PROs) in adults with pediatric-onset HPP. A longitudinal telephone-based survey was administered to eligible individuals enrolled in a patient support program. Interviews were conducted at study entry (prior to asfotase alfa initiation) and after 3, 6, and 12 months. PROs—Patient Health Questionnaire-9 [PHQ-9], Work Productivity and Activity Impairment–Specific Health Problem [WPAI:SHP], Patient-Reported Outcomes Measurement Information System 29 [PROMIS-29], and Routine Assessment of Patient Index Data 3 [RAPID3]—were assessed at each time point. Appropriate statistical tests were performed to assess score changes. Among 50 enrolled patients (mean age: 46 years [SD: 15.4]; 80% female; 94% white), 49 were evaluable at 3 months, 44 at 6 months, and 29 at 12 months. By Month 3, statistically significant improvements from baseline were detected in PHQ-9 scores (10.6 vs. 5.8 [p < 0.0001]), PROMIS-29 domain scores (overall physical function: 38.0 vs. 43.0 [p = 0.001]; anxiety: 57.5 vs. 51.5 [p = 0.0011]; fatigue: 63.3 vs. 55.3 [p < 0.0001]; sleep disturbances: 58.8 vs. 54.3 [p = 0.0099]; ability to participate in social roles and activities: 42.6 vs. 47.7 [p = 0.0012]; and pain interference: 63.8 vs. 58.4 [p = 0.001]) and RAPID3 domain scores (functional status: 2.7 vs. 1.1 [p < 0.0001]; pain tolerance: 6.0 vs. 3.2 [p < 0.0001]; and global health estimate: 5.1 vs. 2.7 [p < 0.0001]). Improvements persisted at Month 12. Patients also showed improvements in WPAI:SHP domain scores at Month 6 (presenteeism: 39.6% vs. 14.1% [p < 0.0001] and work productivity loss: 41.9% vs. 14.1% [p < 0.0001]). Treatment with asfotase alfa was associated with improved quality of life across several domains.
低磷酸盐血症（HPP）是一种罕见的遗传性代谢性疾病，由组织非特异性碱性磷酸酶活性不足引起。本研究评估了使用阿斯福通α治疗对儿童型HPP成人患者报告结果（PROs）的影响。研究人员通过电话对参加患者支持计划的合格患者进行了纵向调查。访谈在研究开始时（开始使用阿斯福太酶α之前）以及 3、6 和 12 个月后进行。在每个时间点都对PROs--患者健康问卷-9 [PHQ-9]、工作效率和活动障碍--特定健康问题[WPAI:SHP]、患者报告结果测量信息系统29 [PROMIS-29]和患者指数数据常规评估3 [RAPID3]进行了评估。对评分变化进行了适当的统计检验。在 50 名入组患者中（平均年龄：46 岁 [标码：15.4]；80% 为女性；94% 为白人），49 人在 3 个月时接受了评估，44 人在 6 个月时接受了评估，29 人在 12 个月时接受了评估。到第 3 个月时，PHQ-9 评分（10.6 vs. 5.8 [p < 0.0001]）、PROMIS-29 领域评分（总体身体功能：38.0 vs. 43.0 [p<0.0001]）与基线相比均有统计学意义上的显著改善：63.3 vs. 55.3 [p < 0.0001]；睡眠障碍：58.8 vs. 54.3 [p = 0.0099]；参与社会角色和活动的能力：42.6 vs. 47.7 [p = 0.0012]；疼痛干扰：63.8 vs. 58.4 [p = 0.001]）和 RAPID3 领域得分（功能状态：2.7 vs. 1.1 [p < 0.0001]；疼痛耐受性：6.0 vs. 3.2 [p < 0.0001]；总体健康估计：5.1 vs. 2.7 [p < 0.0001]）。这些改善在第 12 个月仍在持续。第 6 个月时，患者的 WPAI:SHP 领域得分也有所改善（缺勤率：39.6% vs. 14.0% [p < 0.0001]）：39.6% vs. 14.1% [p < 0.0001]）和工作效率损失（41.9% vs. 14.1% [p < 0.0001]）：41.9% vs. 14.1% [p < 0.0001]）。阿斯福通α治疗与多个领域的生活质量改善相关。
{"title":"Improvement in quality of life after Asfotase Alfa treatment in adults with Pediatric-onset Hypophosphatasia: data from 5 patient-reported outcome measures","authors":"K. Dahir, Steven W Ing, Chad Deal, Andrew Messali, Toby Bates, E. Rush","doi":"10.1093/jbmrpl/ziae062","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae062","url":null,"abstract":"\u0000 Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. This study assessed the impact of treatment with asfotase alfa on patient-reported outcomes (PROs) in adults with pediatric-onset HPP. A longitudinal telephone-based survey was administered to eligible individuals enrolled in a patient support program. Interviews were conducted at study entry (prior to asfotase alfa initiation) and after 3, 6, and 12 months. PROs—Patient Health Questionnaire-9 [PHQ-9], Work Productivity and Activity Impairment–Specific Health Problem [WPAI:SHP], Patient-Reported Outcomes Measurement Information System 29 [PROMIS-29], and Routine Assessment of Patient Index Data 3 [RAPID3]—were assessed at each time point. Appropriate statistical tests were performed to assess score changes. Among 50 enrolled patients (mean age: 46 years [SD: 15.4]; 80% female; 94% white), 49 were evaluable at 3 months, 44 at 6 months, and 29 at 12 months. By Month 3, statistically significant improvements from baseline were detected in PHQ-9 scores (10.6 vs. 5.8 [p < 0.0001]), PROMIS-29 domain scores (overall physical function: 38.0 vs. 43.0 [p = 0.001]; anxiety: 57.5 vs. 51.5 [p = 0.0011]; fatigue: 63.3 vs. 55.3 [p < 0.0001]; sleep disturbances: 58.8 vs. 54.3 [p = 0.0099]; ability to participate in social roles and activities: 42.6 vs. 47.7 [p = 0.0012]; and pain interference: 63.8 vs. 58.4 [p = 0.001]) and RAPID3 domain scores (functional status: 2.7 vs. 1.1 [p < 0.0001]; pain tolerance: 6.0 vs. 3.2 [p < 0.0001]; and global health estimate: 5.1 vs. 2.7 [p < 0.0001]). Improvements persisted at Month 12. Patients also showed improvements in WPAI:SHP domain scores at Month 6 (presenteeism: 39.6% vs. 14.1% [p < 0.0001] and work productivity loss: 41.9% vs. 14.1% [p < 0.0001]). Treatment with asfotase alfa was associated with improved quality of life across several domains.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141001986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saija Mikkilä, B. Handegård, Jonas Johansson, L. Hopstock, Roland van den Tillaar, N. Emaus, B. Morseth, Boye Welde
Positive associations between physical activity and bone health have been found in population-based studies, however, mostly based on self-reported physical activity. Therefore, we investigated the association between accelerometer-measured physical activity, measured in steps per day and minutes of moderate to vigorous physical activity (MVPA) per day, and total hip areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry in a general population, utilizing multiple regression models. The study participants, 1560 women and 1177 men aged 40–84 years, were part of the seventh survey of the Tromsø Study (2015–2016). In both genders, we found a positive association between the number of daily steps and aBMD adjusted for age, body mass index (BMI), and smoking status (p < .001). In women, an increase of 1000 steps per day was associated with 0.005 g/cm2 higher aBMD. For men, a polynomial curve indicated a positive association with aBMD up to 5000 steps per day, plateauing between 5000 and 14 000 steps, and then increasing again. Additionally, MVPA duration was positively associated with aBMD in both women (p < .001) and men (p = .004) when adjusted for age, BMI, and smoking status. Specifically, each 60-minute increase in daily MVPA was associated with 0.028 g/cm2 and 0.023 g/cm2 higher aBMD in women and men, respectively. Despite positive associations, the clinical impact of physical activity on aBMD in this general population of adults and older adults was relatively small, and a large increase in daily MVPA might not be achievable for most individuals. Therefore, further longitudinal population-based studies, incorporating device-based measures of physical activity could add more clarity to these relationships.
{"title":"Cross-sectional associations between accelerometer-measured physical activity and hip bone mineral density. The Tromsø study 2015–2016","authors":"Saija Mikkilä, B. Handegård, Jonas Johansson, L. Hopstock, Roland van den Tillaar, N. Emaus, B. Morseth, Boye Welde","doi":"10.1093/jbmrpl/ziae061","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae061","url":null,"abstract":"\u0000 Positive associations between physical activity and bone health have been found in population-based studies, however, mostly based on self-reported physical activity. Therefore, we investigated the association between accelerometer-measured physical activity, measured in steps per day and minutes of moderate to vigorous physical activity (MVPA) per day, and total hip areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry in a general population, utilizing multiple regression models. The study participants, 1560 women and 1177 men aged 40–84 years, were part of the seventh survey of the Tromsø Study (2015–2016).\u0000 In both genders, we found a positive association between the number of daily steps and aBMD adjusted for age, body mass index (BMI), and smoking status (p < .001). In women, an increase of 1000 steps per day was associated with 0.005 g/cm2 higher aBMD. For men, a polynomial curve indicated a positive association with aBMD up to 5000 steps per day, plateauing between 5000 and 14 000 steps, and then increasing again. Additionally, MVPA duration was positively associated with aBMD in both women (p < .001) and men (p = .004) when adjusted for age, BMI, and smoking status. Specifically, each 60-minute increase in daily MVPA was associated with 0.028 g/cm2 and 0.023 g/cm2 higher aBMD in women and men, respectively.\u0000 Despite positive associations, the clinical impact of physical activity on aBMD in this general population of adults and older adults was relatively small, and a large increase in daily MVPA might not be achievable for most individuals. Therefore, further longitudinal population-based studies, incorporating device-based measures of physical activity could add more clarity to these relationships.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141010762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dorina Condurache, Stefania D’angelo, Ahmed M. Salih, Liliana Szabo, C. Mccracken, Adil Mahmood, Elizabeth M Curtis, André Altmann, Steffen E Petersen, N. C. Harvey, Z. Raisi-Estabragh
This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: 1) prevalent and incident cardiovascular diseases (CVDs: ischaemic heart disease (IHD), myocardial infarction (MI), heart failure, non-ischaemic cardiomyopathy (NICM), arrhythmia), 2) mortality (all-cause, CVD, IHD), and 3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank. Clinical outcomes were ascertained using health record linkage over 12.3 years of prospective follow-up. Two-sample Mendelian randomization (MR) was conducted to assess causal associations between BMD and CMR metrics using genetic instrumental variables identified from published genome-wide association studies. The analysis included 485 257 participants (55% women, mean age 56.5 ± 8.1 years). Higher heel eBMD was associated with lower odds of all prevalent CVDs considered. The greatest magnitude of effect was seen in association with heart failure and NICM, where 1-SD increase in eBMD was associated with 15% lower odds of heart failure and 16% lower odds of NICM. Association between eBMD and incident IHD and MI were non-significant; the strongest relationship was with incident heart failure (SHR: 0.90 [95% CI: 0.89-0.92]). Higher eBMD was associated with a decreased risk in all-cause, CVD, and IHD mortality, in the fully adjusted model. Higher eBMD was associated with greater aortic distensibility; associations with other CMR metrics were null. Higher heel eBMD is linked to reduced risk of a range of prevalent and incident CVD and mortality outcomes. While observational analyses suggest associations between higher eBMD and greater aortic compliance, MR analysis did not support a causal relationship between genetically predicted BMD and CMR phenotypes. These findings support the notion that bone-cardiovascular associations reflect shared risk factors/mechanisms rather than direct causal pathways.
{"title":"Bone health, cardiovascular disease and imaging outcomes in UK biobank: a causal analysis","authors":"Dorina Condurache, Stefania D’angelo, Ahmed M. Salih, Liliana Szabo, C. Mccracken, Adil Mahmood, Elizabeth M Curtis, André Altmann, Steffen E Petersen, N. C. Harvey, Z. Raisi-Estabragh","doi":"10.1093/jbmrpl/ziae058","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae058","url":null,"abstract":"\u0000 This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: 1) prevalent and incident cardiovascular diseases (CVDs: ischaemic heart disease (IHD), myocardial infarction (MI), heart failure, non-ischaemic cardiomyopathy (NICM), arrhythmia), 2) mortality (all-cause, CVD, IHD), and 3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank.\u0000 Clinical outcomes were ascertained using health record linkage over 12.3 years of prospective follow-up. Two-sample Mendelian randomization (MR) was conducted to assess causal associations between BMD and CMR metrics using genetic instrumental variables identified from published genome-wide association studies.\u0000 The analysis included 485 257 participants (55% women, mean age 56.5 ± 8.1 years). Higher heel eBMD was associated with lower odds of all prevalent CVDs considered. The greatest magnitude of effect was seen in association with heart failure and NICM, where 1-SD increase in eBMD was associated with 15% lower odds of heart failure and 16% lower odds of NICM. Association between eBMD and incident IHD and MI were non-significant; the strongest relationship was with incident heart failure (SHR: 0.90 [95% CI: 0.89-0.92]). Higher eBMD was associated with a decreased risk in all-cause, CVD, and IHD mortality, in the fully adjusted model. Higher eBMD was associated with greater aortic distensibility; associations with other CMR metrics were null.\u0000 Higher heel eBMD is linked to reduced risk of a range of prevalent and incident CVD and mortality outcomes. While observational analyses suggest associations between higher eBMD and greater aortic compliance, MR analysis did not support a causal relationship between genetically predicted BMD and CMR phenotypes. These findings support the notion that bone-cardiovascular associations reflect shared risk factors/mechanisms rather than direct causal pathways.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Britt Opdebeeck, Astrid Van den Branden, Saar Adriaensen, I. Orriss, J. Patel, Hilde Geryl, Kathleen Zwijsen, P. D’Haese, A. Verhulst
Arterial media calcification or pathological deposition of calcium-phosphate crystals in the vessel wall contributes significantly to the high mortality rate observed in patients with chronic kidney disease (CKD). Extracellular nucleotides (i.e. ATP or UTP) regulate the arterial calcification process by interacting with (i) purinergic receptors and (ii) breakdown via ecto-nucleotidases such as NPP1 or NPP3 affecting the local levels of calcification inhibitor, pyrophosphate, and –stimulator inorganic phosphate (PPi/Pi ratio). Also, it has been shown that ATP analogs (i.e. β,γ-meATP) inhibit vascular smooth muscle cell calcification in vitro. In the first experiment, daily dosing of β,γ-meATP (2 mg/kg) was investigated in rats, receiving a warfarin diet to trigger the development of non-CKD related arterial medial calcifications. This study showed that β,γ-meATP significantly lowered the calcium scores in the aorta and peripheral vessels in warfarin-exposed rats. In a second experiment, daily dosing of 4 mg/kg β,γ-meATP, and its metabolite medronic acid (MDP) was analyzed in rats receiving an adenine diet to promote the development of CKD-related arterial medial calcification. β,γ-meATP, and MDP did not significantly decrease aortic calcification scores in this model. Moreover, both compounds induced deleterious effects on physiological bone mineralization causing an imminent risk for worsening the already compromised bone status in CKD. Due to this, it was not possible to raise the dosage of both compounds to tackle CKD-related arterial calcification. Again, this points out the difficult task; targeting solely ectopic calcifications without negatively affecting physiological bone mineralization. On the other hand, aortic mRNA expression of Enpp1 and Enpp3 was significantly and positively associated with aortic calcification scores, suggesting that normalizing the aortic NPP1/3 activity to control values might be a possible target to treat (CKD-induced) arterial media calcifications.
{"title":"β,γ-methylene-ATP and its metabolite medronic acid affect both arterial media calcification and bone mineralization in non-CKD and CKD ratso","authors":"Britt Opdebeeck, Astrid Van den Branden, Saar Adriaensen, I. Orriss, J. Patel, Hilde Geryl, Kathleen Zwijsen, P. D’Haese, A. Verhulst","doi":"10.1093/jbmrpl/ziae057","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae057","url":null,"abstract":"\u0000 Arterial media calcification or pathological deposition of calcium-phosphate crystals in the vessel wall contributes significantly to the high mortality rate observed in patients with chronic kidney disease (CKD). Extracellular nucleotides (i.e. ATP or UTP) regulate the arterial calcification process by interacting with (i) purinergic receptors and (ii) breakdown via ecto-nucleotidases such as NPP1 or NPP3 affecting the local levels of calcification inhibitor, pyrophosphate, and –stimulator inorganic phosphate (PPi/Pi ratio). Also, it has been shown that ATP analogs (i.e. β,γ-meATP) inhibit vascular smooth muscle cell calcification in vitro. In the first experiment, daily dosing of β,γ-meATP (2 mg/kg) was investigated in rats, receiving a warfarin diet to trigger the development of non-CKD related arterial medial calcifications. This study showed that β,γ-meATP significantly lowered the calcium scores in the aorta and peripheral vessels in warfarin-exposed rats. In a second experiment, daily dosing of 4 mg/kg β,γ-meATP, and its metabolite medronic acid (MDP) was analyzed in rats receiving an adenine diet to promote the development of CKD-related arterial medial calcification. β,γ-meATP, and MDP did not significantly decrease aortic calcification scores in this model. Moreover, both compounds induced deleterious effects on physiological bone mineralization causing an imminent risk for worsening the already compromised bone status in CKD. Due to this, it was not possible to raise the dosage of both compounds to tackle CKD-related arterial calcification. Again, this points out the difficult task; targeting solely ectopic calcifications without negatively affecting physiological bone mineralization. On the other hand, aortic mRNA expression of Enpp1 and Enpp3 was significantly and positively associated with aortic calcification scores, suggesting that normalizing the aortic NPP1/3 activity to control values might be a possible target to treat (CKD-induced) arterial media calcifications.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140677671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-20eCollection Date: 2024-05-01DOI: 10.1093/jbmrpl/ziae043
Alexandra Kachaner, Raphaèle Seror, Fleur Cohen Aubart, Julien Henry, Thierry Lazure, Jean François Emile, Xavier Mariette, Samuel Bitoun
Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH.
{"title":"Complete remission after a single bisphosphonate infusion in isolated bone Langerhans cell histiocytosis lesion: a case report and a narrative review of the literature.","authors":"Alexandra Kachaner, Raphaèle Seror, Fleur Cohen Aubart, Julien Henry, Thierry Lazure, Jean François Emile, Xavier Mariette, Samuel Bitoun","doi":"10.1093/jbmrpl/ziae043","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae043","url":null,"abstract":"<p><p>Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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