Messages from the Mineral: How Bone Cells Communicate with Other Tissues
AbstractBone is a highly dynamic tissue, and the constant actions of bone-forming and bone-resorbing cells are responsible for attaining peak bone mass, maintaining bone mass in the adults, and the subsequent bone loss with aging and menopause, as well as skeletal complications of diseases and drug side-effects. It is now accepted that the generation and activity of bone-forming osteoblasts and bone-resorbing osteoclasts is modulated by osteocytes, osteoblast-derived cells embedded in the bone matrix. The interaction among bone cells occurs through direct contact and via secreted molecules. In addition to the regulation of...
Source: Calcified Tissue International - May 12, 2023 Category: Orthopaedics Source Type: research
Radial HR-pQCT and Finite Element Analysis in HPP Patients are Superior in Identifying Susceptibility to Fracture-Associated Skeletal Affections Compared to DXA and Laboratory Tests
AbstractHypophosphatasia (HPP) is an inborn disease that causes a rare form of osteomalacia, a mineralization disorder affecting mineralized tissues. Identification of patients at high risk for fractures or other skeletal manifestations (such as insufficiency fractures or excessive bone marrow edema) by bone densitometry and laboratory tests remains clinically challenging. Therefore, we examined two cohorts of patients with variants in theALPL gene grouped by bone manifestations. These groups were compared by means of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT) and sim...
Source: Calcified Tissue International - May 6, 2023 Category: Orthopaedics Source Type: research
Regulation of the Osteocyte Secretome with Aging and Disease
AbstractAs the most numerous and long-lived of all bone cells, osteocytes have essential functions in regulating skeletal health. Through the lacunar-canalicular system, secreted proteins from osteocytes can reach cells throughout the bone. Furthermore, the intimate connectivity between the lacunar-canalicular system and the bone vasculature allows for the transport of osteocyte-secreted factors into the circulation to reach the entire body. Local and endocrine osteocyte signaling regulates physiological processes such as bone remodeling, bone mechanoadaptation, and mineral homeostasis. However, these processes are disrupt...
Source: Calcified Tissue International - May 6, 2023 Category: Orthopaedics Source Type: research
NMP4, an Arbiter of Bone Cell Secretory Capacity and Regulator of Skeletal Response to PTH Therapy
AbstractThe skeleton is a secretory organ, and the goal of some osteoporosis therapies is to maximize bone matrix output.Nmp4 encodes a novel transcription factor that regulates bone cell secretion as part of its functional repertoire. Loss ofNmp4 enhances bone response to osteoanabolic therapy, in part, by increasing the production and delivery of bone matrix.Nmp4 shares traits with scaling factors, which are transcription factors that influence the expression of hundreds of genes to govern proteome allocation for establishing secretory cell infrastructure and capacity.Nmp4 is expressed in all tissues and while global los...
Source: Calcified Tissue International - May 6, 2023 Category: Orthopaedics Source Type: research
Radial HR-pQCT and Finite Element Analysis in HPP Patients are Superior in Identifying Susceptibility to Fracture-Associated Skeletal Affections Compared to DXA and Laboratory Tests
AbstractHypophosphatasia (HPP) is an inborn disease that causes a rare form of osteomalacia, a mineralization disorder affecting mineralized tissues. Identification of patients at high risk for fractures or other skeletal manifestations (such as insufficiency fractures or excessive bone marrow edema) by bone densitometry and laboratory tests remains clinically challenging. Therefore, we examined two cohorts of patients with variants in theALPL gene grouped by bone manifestations. These groups were compared by means of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT) and sim...
Source: Calcified Tissue International - May 6, 2023 Category: Orthopaedics Source Type: research
Regulation of the Osteocyte Secretome with Aging and Disease
AbstractAs the most numerous and long-lived of all bone cells, osteocytes have essential functions in regulating skeletal health. Through the lacunar-canalicular system, secreted proteins from osteocytes can reach cells throughout the bone. Furthermore, the intimate connectivity between the lacunar-canalicular system and the bone vasculature allows for the transport of osteocyte-secreted factors into the circulation to reach the entire body. Local and endocrine osteocyte signaling regulates physiological processes such as bone remodeling, bone mechanoadaptation, and mineral homeostasis. However, these processes are disrupt...
Source: Calcified Tissue International - May 6, 2023 Category: Orthopaedics Source Type: research
NMP4, an Arbiter of Bone Cell Secretory Capacity and Regulator of Skeletal Response to PTH Therapy
AbstractThe skeleton is a secretory organ, and the goal of some osteoporosis therapies is to maximize bone matrix output.Nmp4 encodes a novel transcription factor that regulates bone cell secretion as part of its functional repertoire. Loss ofNmp4 enhances bone response to osteoanabolic therapy, in part, by increasing the production and delivery of bone matrix.Nmp4 shares traits with scaling factors, which are transcription factors that influence the expression of hundreds of genes to govern proteome allocation for establishing secretory cell infrastructure and capacity.Nmp4 is expressed in all tissues and while global los...
Source: Calcified Tissue International - May 6, 2023 Category: Orthopaedics Source Type: research
Nonresponder Considerations for Romosozumab Treatment
This study aimed to identify risk factors for being a nonresponder to romosozumab treatment. This retrospective observational study included 92 patients. Romosozumab (210 mg) was subcutaneously administered to the participants every 4 weeks over 12 months. We excluded patients who previously underwent treatment for osteoporosis to assess the impact of romosozumab alone. We evaluated the proportion of patients who did not respond to romosozumab treatment to the lu mbar spine and hip with increased BMD. Nonresponders were defined as those with a bone density change of < 3% after 12 months of treatment. We compar...
Source: Calcified Tissue International - May 3, 2023 Category: Orthopaedics Source Type: research
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and the Risk of Fracture: A Systematic Review and Meta-analysis of Randomized Controlled Trials
AbstractOsteoporosis and hyperlipidemia are closely correlated and statins might be associated with a decreased risk of fracture. We aimed to investigate the association between proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) therapy and the risk of fracture. The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to October 22, 2022. Randomized clinical trials (RCTs) that addressed to fracture events of participants using alirocumab, evolocumab, bococizumab or inclisiran, with a follow-up of ≥ 24 weeks were included. Meta-analyses were conducted to...
Source: Calcified Tissue International - April 26, 2023 Category: Orthopaedics Source Type: research
Bisphosphonate FYB-931 Prevents High Phosphate-Induced Vascular Calcification in Rat Aortic Rings by Altering the Dynamics of the Transformation of Calciprotein Particles
In conclusion, treatment with FYB-931 prevents high phosphate-induced rat aortic vascular calcification by altering the dynamics of CPP transformation. This finding suggests that inhibition of the transformation from primary to secondary CPPs is an important target for the prevention of vascular calcification in patients with chronic kidney disease. (Source: Calcified Tissue International)
Source: Calcified Tissue International - April 26, 2023 Category: Orthopaedics Source Type: research
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and the Risk of Fracture: A Systematic Review and Meta-analysis of Randomized Controlled Trials
AbstractOsteoporosis and hyperlipidemia are closely correlated and statins might be associated with a decreased risk of fracture. We aimed to investigate the association between proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) therapy and the risk of fracture. The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to October 22, 2022. Randomized clinical trials (RCTs) that addressed to fracture events of participants using alirocumab, evolocumab, bococizumab or inclisiran, with a follow-up of ≥ 24 weeks were included. Meta-analyses were conducted to...
Source: Calcified Tissue International - April 26, 2023 Category: Orthopaedics Source Type: research
Bisphosphonate FYB-931 Prevents High Phosphate-Induced Vascular Calcification in Rat Aortic Rings by Altering the Dynamics of the Transformation of Calciprotein Particles
In conclusion, treatment with FYB-931 prevents high phosphate-induced rat aortic vascular calcification by altering the dynamics of CPP transformation. This finding suggests that inhibition of the transformation from primary to secondary CPPs is an important target for the prevention of vascular calcification in patients with chronic kidney disease. (Source: Calcified Tissue International)
Source: Calcified Tissue International - April 26, 2023 Category: Orthopaedics Source Type: research
