Modeling and simulation of bone mineral density in Japanese osteoporosis patients treated with zoledronic acid using tartrate-resistant acid phosphatase 5b, a bone resorption marker

Mori, Yoko; Kasai, Hidefumi; Ose, Atsushi; Serada, Masashi; Ishiguro, Makio; Shiraki, Masataka

doi:10.1007/s00198-018-4376-1

Cited by 19 publications

(20 citation statements)

References 22 publications

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“…These findings point to a generalized reduction in pro-osteoblastic activity in CRSwNP. Furthermore, our results show that tartrate-resistant ACP5, a bone resorption marker, 42 is significantly increased. ACP5 is a functional protein utilized by osteoclasts to remove bone, 43 and high ACP5 expression has been previously associated with increased rates of bone turnover.…”

Section: Discussionsupporting

confidence: 50%

“…Similarly, KOS was inversely correlated with the levels of BMPR1A and CRDL1. As a negative regulator of bone formation 43 and marker of bone resorption, 42 the level of ACP5 significantly and positively correlated with osteitis scores. Taken together, these findings cast a new light on osteitis and neo-osteogenesis in CRSwNP, suggesting that the underlying mechanism is one of dysregulated bone turnover as opposed to enhanced bone production.…”

Section: Discussionmentioning

confidence: 99%

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Osteitis is associated with dysregulated pro‐osteoblastic activity in patients with nasal polyps

Nocera

Müller

et al. 2018

The Laryngoscope

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Objectives/Hypothesis The overlying inflammatory mucosa plays a crucial role in the initiation of osteitis; however, the molecular mechanism is unclear. The objective of this study was to explore the bone morphogenetic protein (BMP) pathway and to correlate the expression of key signaling molecules with the degree of osteitis in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Study Design Prospective experimental analysis. Methods This was an institutional review board–approved study in which mucosal samples were obtained from sites of osteitis in CRSwNP and compared to nonosteitic healthy controls (n = 10/group). Protein expression of key BMP pathway was quantified by aptamer‐based protein array and confirmed by a set of selected mRNA analyses. Degree of osteitis was assessed using both Kennedy Osteitis Score and Global Osteitis Score (GOS). Results Pro‐osteoblastic expression of BMP7 (fold change [FC] = −1.18, P = .017) and BMP9 (FC = −1.32, P = .023), their receptors, BMP receptor type‐1A (BMPR1A) (FC = −2.56, P = .005) and BMP receptor type‐2 (FC = −1.28, P = .022), and two enhancers of BMP signaling pathway, the repulsive guidance molecule domain family member B (FC = −1.13, P = .008) and the chordin‐like protein 1 (FC = −1.18, P = .027), were all significantly downregulated in CRSwNP. Conversely, the pro‐osteoclastic factor, tartrate‐resistant acid phosphatase type 5 (ACP5) (FC = 2.36, P = .001), was significantly increased in CRSwNP. GOS was inversely correlated with levels of BMP7 (r = −0.684, P = .005) and BMPR1A (r = −0.864, P = .005) and positively correlated with levels of ACP5 (r = 0.815, P = .004). The FCs among the proteins studied significantly and positively correlated with the FCs of their mRNA expression (r = 0.908, P = .002). Conclusions Downregulated pro‐osteoblastic mucosal BMP signaling is strongly and significantly associated with increased osteitis in CRSwNP. Level of Evidence NA Laryngoscope, 129:E102–E109, 2019

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Osteitis is associated with dysregulated pro‐osteoblastic activity in patients with nasal polyps

Nocera

Müller

et al. 2018

The Laryngoscope

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“…Osteoblasts synthesize osteogenic markers, such as osteocalcin, ALP, and PINP, which reflect the osteogenic function of the body [34]. CTX-1 and TRACP 5b are markers of bone resorption [35,36,37], the higher the levels of TRACP 5b and CTX-1, the lower the bone mineral density [38,39,40]. In this study, both the markers of bone formation and bone resorption were increased in diabetic rats, indicating that the bone turnover was increased.…”

Section: Discussionmentioning

confidence: 99%

Icariin Prevents Diabetes-Induced Bone Loss in Rats by Reducing Blood Glucose and Suppressing Bone Turnover

Zheng

et al. 2019

Molecules

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Diabetic Osteoporosis (DOP) is a common metabolic bone disease, characterized by decreased bone mineral density (BMD) and destruction of bone microstructure. It has been reported that icariin is beneficial for estrogen deficiency-induced osteoporosis, and alcohol-induced osteoporosis; whether icariin has protective effects on diabetes-induced osteoporosis has not been reported. In this study, a rat model of diabetic osteoporosis was established by streptozotocin injection, the bone protective effects and potential mechanism of icariin on diabetes-induced bone loss was observed. Thirty 8-week-old female Sprague Dawley rats were divided into control group (vehicle treatment), T1DM (diabetic) group and T1DM-icariin (ICA) group (diabetic rats treated with icariin), 10 rats in each group. The bone histomorphometry parameters, bone mineral density (BMD), serum bone turnover markers, and bone marrow adipogenesis were analyzed after 8 weeks of icariin administration. The results showed consumption of icariin at a doses of 100 mg kg−1 decreased blood glucose, and increased the BMD of diabetic rats. Icariin effectively decreased serum bone turnover marker levels, including CTX-1, ALP, TRACP 5b, osteocalcin, and PINP. Meanwhile, the bone histomorphometry parameters, the number of osteoclasts per bone perimeter were turned to be normal level, and the icariin treatment suppressed bone marrow adipogenesis. The runt-related transcription factor 2 (RUNX 2), as well as the osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) ratio in serum and bone tissues were increased significantly after icariin treatment in diabetic rats. All of the above indicate that oral administration of icariin can prevent diabetic osteoporosis; the effect is mainly related to its ability to reduce blood glucose, inhibit bone turnover and bone marrow adipogenesis, as well as up-regulate bone RUNX 2, and OPG expression.

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“…for osteoporosis can be predicted from bone turnover markers. [21][22][23][24] Thus, a twice-weekly 28.2-μg injection is expected to have comparable efficacy to that of the once-weekly 56.5-μg injection, with the dosing interval being irrelevant to this efficacy. Subject demographics were similar among each cohort and group; however, the values of 25hydroxyvitamin D 3 at baseline in subjects in Cohort 1 were relatively low in comparison with subjects in other cohorts ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

Safety Profiles, Pharmacokinetics, and Changes in Bone Turnover Markers After Twice‐Weekly Subcutaneous Administration of Teriparatide in Healthy Japanese Postmenopausal Women: A Single‐Blind Randomized Study

Kumagai

Ose

Tanaka

et al. 2019

Clinical Pharm in Drug Dev

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Once-weekly injection of 56.5-μg teriparatide formulation is a potent therapeutic agent for osteoporosis treatment. However, this treatment has an issue of difficulty in continuing the treatment by its adverse side effects including nausea, vomiting, and headaches. To reduce these adverse side effects, we conducted a randomized, single-blind, placebocontrolled study to examine the pharmacokinetics, changes in bone turnover markers, and safety profiles of twice-weekly 28.2-μg teriparatide injections. Different dosing intervals of the twice-weekly 28.2-μg injections were also studied. A total of 100 healthy Japanese postmenopausal women were enrolled in this multiple-dosing study. The systemic exposure of teriparatide acetate in the twice-weekly 28.2-μg injection was half that of the once-weekly 56.5-μg injection. Changes in bone turnover markers in the twice-weekly 28.2-μg injection were comparable to those in the once-weekly 56.5-μg injection. Incidences of adverse events including nausea, vomiting, and headaches were lower in the twice-weekly 28.2-μg injections than those in the once-weekly 56.5-μg injection. Findings were similar in the twice-weekly 28.2-μg injections regardless of the dosing interval. Thus, the new dosing regimen using twice-weekly 28.2-μg injections maintained comparable efficacy to the once-weekly 56.5-μg injections; however, it improved the safety profile and contributed to better continuity of care with teriparatide.

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Modeling and simulation of bone mineral density in Japanese osteoporosis patients treated with zoledronic acid using tartrate-resistant acid phosphatase 5b, a bone resorption marker

Cited by 19 publications

References 22 publications

Osteitis is associated with dysregulated pro‐osteoblastic activity in patients with nasal polyps

Osteitis is associated with dysregulated pro‐osteoblastic activity in patients with nasal polyps

Icariin Prevents Diabetes-Induced Bone Loss in Rats by Reducing Blood Glucose and Suppressing Bone Turnover

Safety Profiles, Pharmacokinetics, and Changes in Bone Turnover Markers After Twice‐Weekly Subcutaneous Administration of Teriparatide in Healthy Japanese Postmenopausal Women: A Single‐Blind Randomized Study

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