| 1. |
- Abtahi, Jahan, 1965-, et al.
(författare)
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Ibandronate Reduces the Surface Bone Resorption of Mandibular Bone Grafts : A Randomized Trial With Internal Controls
- 2021
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Autologous bone grafts are considered the gold standard for reconstruction of the edentulous alveolar ridges. However, this procedure is associated with unpredictable bone loss caused by physiological bone resorption. Bisphosphonates are antiresorptive drugs that act specifically on osteoclasts, thereby maintaining bone density, volume, and strength. It was hypothesized that the resorption of bone grafts treated with an ibandronate solution would be less advanced than bone grafts treated with saline. Ten patients who underwent bilateral sagittal split osteotomy were included in a randomized double-blind trial with internal controls. Each patient received a bone graft treated with a solution of ibandronate on one side and a graft treated with saline (controls) contralaterally. Radiographs for the measurement of bone volume were obtained at 2 weeks and at 6 months after surgery. The primary endpoint was the difference in the change of bone volume between the control and the ibandronate bone grafts 6 months after surgery. All of the bone grafts healed without complications. One patient was excluded because of reoperation. In eight of the nine patients, the ibandronate bone grafts showed an increase in bone volume compared with baseline, with an average gain of 126 mm(3) (40% more than baseline) with a range of +27 to +218 mm(3). Only one ibandronate-treated graft had a decrease in bone volume (8%). In the controls, an average bone volume loss of -146 mm(3) (58% of baseline) with a range of -29 to -301 mm(3) was seen. In the maxillofacial field, the reconstructions of atrophic alveolar ridges, especially in the esthetical zones, are challenging. These results show that bone grafts locally treated with ibandronate solution increases the remaining bone volume. This might lead to new possibilities for the maxillofacial surgeons in the preservation of bone graft volumes and for dental implant installations.
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| 2. |
- Atanasova, Diana, 1991-, et al.
(författare)
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Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts
- 2024
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Ingår i: JBMR Plus. - : Oxford University Press. - 2473-4039. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has 5 potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303, and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl+/− expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and liquid chromatography with tandem mass spectrometry. The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all 5 sites of TNALP, as well as core fucosylation on 4 out of 5 sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.
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| 3. |
- Desai, S., et al.
(författare)
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A COX-2 Inhibitor Does Not Interfere With the Bone-Protective Effects of Loading in Male Mice With Arthritis
- 2023
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Ingår i: Jbmr Plus. - 2473-4039. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical loading enhances bone strength and counteracts arthritis-induced inflammation-mediated bone loss in female mice. It is unknown whether nonsteroidal anti-inflammatory drugs (NSAIDs; eg, COX-2 inhibitors) can reduce inflammation without affecting the loading-associated bone formation in male mice. The aim of this study was to investigate if loading combined with a COX-2 inhibitor (NS-398) could prevent arthritis-induced bone loss and inflammation in male mice. Four-month-old male C57BL/6J mice were subjected to axial tibial mechanical loading three times/week for 2 weeks. Local mono-arthritis was induced with a systemic injection of methylated bovine serum albumin on the first day of loading, followed by a local injection in one knee 1 week later. The arthritis induction, knee swelling, bone architecture, and osteoclast number were evaluated in the hind limbs. C-terminal cross-links as a marker for osteoclast activity was measured in serum. Compared with loading and arthritis alone, loading of the arthritic joint enhanced swelling that was partly counteracted by NS-398. Loading of the arthritic joint enhanced synovitis and articular cartilage damage compared with loading alone. Loading increased cortical bone and counteracted the arthritis-induced decrease in epiphyseal bone. NS-398 did not alter the bone-protective effects of loading. C-terminal cross-links, a bone resorption marker, was increased by arthritis but not loading. In conclusion, loading prevented arthritis-induced epiphyseal and metaphyseal bone loss, and NS-398 reduced knee swelling without affecting the bone-protective effects of loading. If our results can be extrapolated to the human situation, specific COX-2 inhibitors could be used in combination with loading exercise to prevent pain and swelling of the joint without influencing the bone-protective effects of loading. (c) 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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| 4. |
- Dotevall, Annika, 1957, et al.
(författare)
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Hearing and Balance Exceed Initial Bone Mineral Density in Predicting Incident Fractures: A 25-Year Prospective Observational Study in Menopausal Women With Osteoporosis
- 2022
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Ingår i: Jbmr Plus. - : Wiley. - 2473-4039. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Hearing and balance deteriorate, and fracture incidence increases with age, especially in women. The aim of the present study was to investigate whether impaired hearing and body balance are stronger predictors of fractures than bone mass. Between 1995 and 1997, 80 women, aged 50 to 70 years, with primary osteoporosis, taking menopausal hormone therapy, mainly for menopausal symptoms, participated in a double-blind, randomized, placebo-controlled study of treatment with growth hormone versus placebo. All women received calcium 750 mg and vitamin D 400 U daily. They were then examined yearly until 2007 and followed up by registers until 2020. Hearing was assessed by audiometry. Body balance and fine motor function were tested according to the Bruininks-Oseretsky test. Bone properties were measured with DXA. Data on fractures were derived from the Gothenburg Hospital register. Over the 25-year follow-up, 50 women (63%) sustained 104 fractures, most often related to accidental falls. Thoracic and lumbar spine fractures were most common (36%). Other fractures occurred in the pelvis (14%), humerus (14%), hip (11%), and wrist (10%). Hearing impairment at baseline, measured as pure tone average-high (p = 0.007), pure tone average-mid (p = 0.003), and speech-recognition score (p = 0.025), was associated with a subsequent first fracture, as were worse body balance (p = 0.004), upper limb coordination (p = 0.044), and higher running-speed agility (p = 0.012). After adjustment for age and BMD, pure tone average-high (p = 0.036), pure tone average-mid (p = 0.028), and body balance (p = 0.039) were still significantly associated with incident fractures. Bone mineral content, BMD, and treatment at baseline were not associated with subsequent fracture. In conclusion, hearing and body balance at baseline exceeded initial BMD in predicting incident fractures in osteoporotic women regardless of treatment during 25-year follow-up. (c) 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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| 5. |
- Egund, Lisa, et al.
(författare)
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High Luteinizing Hormone and Lower Levels of Sex Hormones in Younger Men With Distal Radius Fracture
- 2020
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the sex steroid hormone profile in younger men with distal radius fracture (DRF) to elucidate if this could explain the low bone density and osteoporosis previously observed. In a case–control study, 73 men with DRF (mean age 38 ± 9 years; range, 20–51) was compared with 194 age-matched, population controls. Performed assays: total testosterone (TT), calculated free testosterone (cFT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and total estradiol (E2). BMD hip and spine were measured. Fracture cases had lower cFT (298 versus 329 pmol/L; p = 0.008), but not TT, compared with controls. FSH and SHBG were not statistically different. LH was almost 30% higher (5.7 versus 4.5 IU/L; p < 0.001) and a lower E2 was observed (80.0 versus 87.1; p = 0.098). Men with DRF had a lower E2/SHBG ratio compared with controls (2.3 versus 2.9; p = 0.013). A higher proportion of the fracture group had low TT (<10.5 nmol/L; 21% versus 11%; p = 0.052), low cFT (<220 pmol/L; 18% versus 8%; p = 0.017), and low E2 (<73 pmol/L; 48% versus 35%; p = 0.044). Odds ratio (OR) for fracture when having low cFT was 2.3 (95% CI, 1.02–5.49; p = 0.044); with low E2, the OR was 1.7 (95% CI, 0.96–2.96). In this study in young men with DRF exploring sex hormone levels, we find that sex hormone profiles may be disturbed with a lower E2/SHBG ratio, lower cFT, and higher LH. Estrogen is also a strong determinant of bone mass in men; hence, low levels of E2 may be contributing to the observed lower BMD and these differences may be relevant to fracture risk.
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| 6. |
- Harvey, N. C., et al.
(författare)
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Greater pQCT Calf Muscle Density Is Associated with Lower Fracture Risk, Independent of FRAX, Falls and BMD: A Meta-Analysis in the Osteoporotic Fractures in Men (MrOS) Study
- 2022
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the predictive performance of peripheral quantitative computed tomography (pQCT) measures of both calf muscle density (an established surrogate for muscle adiposity, with higher values indicating lower muscle adiposity and higher muscle quality) and size (cross-sectional area [CSA]) for incident fracture. pQCT (Stratec XCT2000/3000) measurements at the tibia were undertaken in Osteoporotic Fractures in Men (MrOS) United States (US), Hong Kong (HK), and Swedish (SW) cohorts. Analyses were by cohort and synthesized by meta-analysis. The predictive value for incident fracture outcomes, illustrated here for hip fracture (HF), using an extension of Poisson regression adjusted for age and follow-up time, was expressed as hazard ratio (HR) per standard deviation (SD) increase in exposure (HR/SD). Further analyses adjusted for femoral neck (fn) bone mineral density (BMD) T-score, Fracture Risk Assessment Tool (FRAX) 10-year fracture probability (major osteoporotic fracture) and prior falls. We studied 991 (US), 1662 (HK), and 1521 (SW) men, mean +/- SD age 77.0 +/- 5.1, 73.9 +/- 4.9, 80 +/- 3.4 years, followed for a mean +/- SD 7.8 +/- 2.2, 8.1 +/- 2.3, 5.3 +/- 2.0 years, with 31, 47, and 78 incident HFs, respectively. Both greater muscle CSA and greater muscle density were associated with a lower risk of incident HF [HR/SD: 0.84; 95% confidence interval [CI], 0.72-1.0 and 0.78; 95% CI, 0.66-0.91, respectively]. The pattern of associations was not materially changed by adjustment for prior falls or FRAX probability. In contrast, after inclusion of fn BMD T-score, the association for muscle CSA was no longer apparent (1.04; 95% CI, 0.88-1.24), whereas that for muscle density was not materially changed (0.69; 95% CI, 0.59-0.82). Findings were similar for osteoporotic fractures. pQCT measures of greater calf muscle density and CSA were both associated with lower incidence of fractures in older men, but only muscle density remained an independent risk factor for fracture after accounting for fn BMD. These findings demonstrate a complex interplay between measures of bone, muscle size, and quality, in determining fracture risk. (C) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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| 7. |
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| 8. |
- Jackmann, Natalja, et al.
(författare)
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Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases
- 2024
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Ingår i: JBMR PLUS. - : OXFORD UNIV PRESS. - 2473-4039. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease. This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2-17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen. Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes -45 degrees and 45 degrees. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure. In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.
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| 9. |
- Jackmann, Natalja, 1968-, et al.
(författare)
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Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases
- 2024
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Ingår i: JBMR Plus. - : Oxford University Press. - 2473-4039. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease.This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2–17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen.Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes −45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure.In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.
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| 10. |
- Lagerquist, Marie K, et al.
(författare)
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Reduction of Mature B Cells and Immunoglobulins Results in Increased Trabecular Bone
- 2022
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Ingår i: Jbmr Plus. - : Wiley. - 2473-4039. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation has a significant effect on bone remodeling and can result in bone loss via increased stimulation of osteoclasts. Activated immunoglobulins, especially autoantibodies, can increase osteoclastogenesis and are associated with pathological bone loss. Whether immunoglobulins and mature B lymphocytes are important for general bone architecture has not been completely determined. Here we demonstrate, using a transgenic mouse model, that reduction of mature B cells and immunoglobulins leads to increased trabecular bone mass compared to wild-type (WT) littermate controls. This bone effect is associated with a decrease in the number of osteoclasts and reduced bone resorption, despite decreased expression of osteoprotegerin. We also demonstrate that the reduction of mature B cells and immunoglobulins do not prevent bone loss caused by estrogen deficiency or arthritis compared to WT littermate controls. In conclusion, the reduction of mature B cells and immunoglobulins results in disturbed regulation of trabecular bone turnover in healthy conditions but is dispensable for pathological bone loss. (c) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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