Bone Reports最新文献

Osteoporosis occurs in every third individual after simultaneous pancreas kidney transplantation (SPKT). Currently used bone measures insufficiently predict their fracture risk. Lumbar spine Trabecular bone score (TBS) and distal radius areal and volumetric bone mineral density (BMD) were monitored for the first time in patients with type 1 diabetes and chronic renal failure after SPKT with steroid-sparing protocol. In 33 subjects (mean age 43.4 ± 9.8 years), dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were performed just after SPKT (baseline) and one and three years later. While TBS Z-scores increased (−1.1 ± 1.2 and −0.3 ± 1.0; p˂0.001, at baseline and year three, respectively), trabecular volumetric BMD Z-scores at distal radius metaphysis did not change during the study (−1.3 ± 1.3 and −1.3 ± 1.0; p = 0.38). Similarly, areal BMD Z-scores increased at lumbar spine, total hip and femoral neck (all p < 0.01), but not at the distal radius. SPKT induced bone measures' improvement at lumbar spine and hip but not at distal radius. Before suggesting changes in current clinical care, predictive value of individual bone measures or its combination for fracture risk assessment remains to be elucidated.

Osteolyses are common findings in elderly patients and most frequently represent malignant or locally aggressive bone tumors, infection, inflammatory and endocrine disorders, histiocytoses, and rare diseases such as Gorham-Stout syndrome. We here report on a novel entity of massive multifocal osteolyses in both shoulders, the right hip and left knee joint and the dens of an 83-year-old patient not relatable to any previously known etiopathology of bone disorders. The soft tissue mass is of myxoid stroma with an unspecific granulomatous inflammatory process, aggressively destroying extensive cortical and cancellous bone segments and encroaching on articulating bones in diarthrodial large joints. Radiological, nuclear medical, serological, histological, and immunohistochemical analyses were incapable of further classifying the disease pattern within the existing scheme of pathology. Quantitative polymerase chain reaction and next generation sequencing revealed that mutations are not suggestive of any known hereditary or acquired bone disease. Possible treatment options include radionuclide therapy for pain palliation and percutaneous radiation to arrest bone resorption while surgical treatment is inevitable for pathological fractures. This case study shall increase the awareness of the musculoskeletal community and motivate to collect further information on this rare but mutilating disorder.

Osteogenesis imperfecta (OI) is a rare hereditary disorder characterized by bone fragility and frequent fractures. While most cases are attributed to variations in collagen-coding genes COL1A1 and COL1A2, other genes such as IFITM5 have also been associated with the disease, accounting for up to 5 % of cases. Here, we report a case of a 3-month-old female with a femur fracture and limb deformity. X-rays revealed evidence of osteopenia and previous fractures in the arms, clavicle, ribs, and left limb, alongside prenatal bone deformities detected by ultrasound. Initial clinical evaluation suggested progressively deforming (Sillence's type III) osteogenesis imperfecta (OI). Molecular testing led to the diagnosis of IFITM5-related OI, identifying the c.-14C>T (rs587776916) variant. Although this variant has been previously reported in patients with IFITM5-related OI, prenatal involvement had not been associated with this variant.

Acid transport is required for bone synthesis by osteoblasts. The osteoblast basolateral surface extrudes acid by Na⁺/H⁺ exchange, but apical proton uptake is undefined. We found high expression of the Cl⁻/H⁺ exchanger ClC3 at the bone apical surface. In mammals ClC3 functions in intracellular vesicular chloride transport, but when we found Cl⁻ dependency of H⁺ transport in osteoblast membranes, we queried whether ClC3 Cl⁻/H⁺ exchange functions in bone formation. We used ClC3 knockout animals, and closely-related ClC5 knockout animals: In vitro studies suggested that both ClC3 and ClC5 might support bone formation. Genotypes were confirmed by total exon sequences. Expression of ClC3, and to a lesser extent of ClC5, at osteoblast apical membranes was demonstrated by fluorescent antibody labeling and electron microscopy with nanometer gold labeling. Animals with ClC3 or ClC5 knockouts were viable. In ClC3 or ClC5 knockouts, bone formation decreased ~40 % by calcein and xylenol orange labeling in vivo. In very sensitive micro-computed tomography, ClC5 knockout reduced bone relative to wild type, consistent with effects of ClC3 knockout, but varied with specific histological parameters. Regrettably, ClC5-ClC3 double knockouts are not viable, suggesting that ClC3 or ClC5 activity are essential to life. We conclude that ClC3 has a direct role in bone formation with overlapping but probably slightly smaller effects of ClC5. The mechanism in mineral formation might include ClC H⁺ uptake, in contrast to ClC3 and ClC5 function in cell vesicles or other organs.

Introduction

Domino osteoporotic vertebral fracture (OVF) is as a subsequent fracture that develops within 3 months before the initial OVF heals. There is limited evidence regarding the efficacy of osteoanabolic agents on its treatment. This study evaluated the effects of bisphosphonates and anabolic agents teriparatide and romosozumab on subsequent domino OVF.

Methods

This was post hoc analysis of a prospective, multicenter, observational study conducted across 8 hospitals, enrolling 144 patients with conservatively treated OVF, grouped into patients receiving bisphosphonate (BP, n = 55), teriparatide (TPTD, n = 62), and romosozumab (Romo, n = 27). The primary outcome was the incidence of subsequent OVF at 3 and 12 months, whereas the secondary outcomes included the incidence of pseudoarthrosis and progression of vertebral collapse (VC). Pseudoarthrosis was classified as stable or unstable based on vertebral instability.

Results

The use of osteoanabolic agents did not reduce the incidence of subsequent OVF at 3 and 12 months. There were no significant differences in the background data or type of conservative treatment among the three groups. However, the TPTD and Romo groups had significantly lower rates of unstable pseudarthrosis (p = 0.03). Additionally, there were no significant differences in VC progression between groups, but it tended to be higher in the BP group than the TPTD and Romo group (p = 0.07).

Conclusion

Osteoanabolic agents were beneficial in reducing unstable pseudoarthrosis, but were not more effective than bisphosphonates in the development of subsequent domino OVF. A more comprehensive approach to the treatment of osteoporosis is needed to prevent domino OVFs.

Spinal cord injury (SCI) leads to significant sublesional bone loss and high fracture rates. While loss of mechanical loading plays a significant role in SCI-induced bone loss, animal studies have demonstrated mechanical loading alone does not fully account for loss of bone following SCI. Indeed, we have shown that bone loss occurs below the level of an incomplete moderate contusion SCI, despite the resumption of weight-bearing and stepping. As systemic factors could also impact bone after SCI, bone alterations may also be present in bone sites above the level of injury. To examine this, we assessed bone microarchitecture and bone turnover in the supralesional humerus in male and female rats at two different ages following a moderate contusion injury in both sub-chronic (30 days) and chronic (180 days) time points after injury. At the 30-day timepoint, we found that both young and adult male SCI rats had decrements in trabecular bone volume at the supralesional proximal humerus (PH), while female SCI rats were not different from age-matched shams. At the 180-day timepoint, there were no statistical differences between SCI and sham groups, irrespective of age or sex, at the supralesional proximal humerus. At the 30-day timepoint, all SCI rats had lower BFR and higher osteoclast-covered trabecular surfaces in the proximal humerus compared to age-matched sham groups generally matching the pattern of SCI-induced changes in bone turnover seen in the sublesional proximal tibia. However, at the 180-day timepoint, only male SCI rats had lower BFR at the supralesional proximal humerus while female SCI rats had higher or no different BFR than their age-matched counterparts. Overall, this preclinical study demonstrates that a moderate contusion SCI leads to alterations in bone turnover above the level of injury within 30-days of injury; however male SCI rats maintained lower BFR in the supralesional humerus into long-term recovery. These data further highlight that bone loss after SCI is not driven solely by disuse. Additionally, these data allude to potential systemic factors exerting influence on bone following SCI and highlight the need to consider treatments for SCI-induced bone loss that impact both sublesional and systemic factors.

Background

Fracture healing poses a significant challenge in orthopedics. Successful regeneration of bone is provided by mechanical stability and a favorable biological microenvironment. This systematic review aims to explore the clinical application of orthobiologics in treating aseptic delayed union and non-union of long bones in adults.

Methods

A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Three databases were explored, with no date restrictions, using keywords related to orthobiologics and delayed union and non-union. Eligible studies included human clinical studies in English, with available full texts, examining orthobiologics such as platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), and bone morphogenetic protein (BMPs) for treating aseptic delayed unions and non-unions in adults. Animal studies, in vitro research, and studies on non-unions due to congenital defects, tumors or infections were excluded.

Results

The initial search identified 9417 studies, with 20 ultimately included in the review. These studies involved 493 patients affected by non-union and 256 patients affected by delayed union, with an average age respectively of 40.62 years and 41.7 years. The mean follow-up period was 15.55 months for non-unions and 8.07 months for delayed unions. PRP was the most used orthobiologic, and outcomes were evaluated through time to union, functional scores, and clinical examinations. The results indicated that orthobiologics, especially PRP, tended to yield better outcomes compared to surgical procedures without biological factors.

Conclusion

This systematic review suggests that orthobiologics, such as PRP, BMPs, and MSCs, can be effective and safe in the management of delayed union and non-union fractures. These biological treatments have the potential to improve union rates, reduce healing times, and enhance functional outcomes in patients with non-union fractures. Further research is essential to refine treatment protocols and determine the most suitable orthobiologic for specific patient populations and fracture types.

Tumor-induced osteomalacia is caused by excessive fibroblast growth factor 23 production mainly from phosphaturic mesenchymal tumors. Surgical excision or tumor ablation are the preferred treatment. Information on bone microarchitecture parameters assessed by high-resolution peripheral quantitative computed tomography is limited. We report a woman with hypophosphatemic osteomalacia with generalized pain, weakness and recurrent fractures, and a large thoracic vertebral mass extending to the posterior mediastinum. Detailed radiologic and histopathologic evaluation revealed a phosphaturic mesenchymal tumor. Two surgeries were necessary for complete removal of the mass. Clinical symptoms improved after attaining normophosphatemia. Four-year post-surgical HR-pQCT parameters, compared to baseline, showed in the left distal radius, stable trabecular and cortical volumetric bone mineral density although below reference range. There was stability of trabecular number and thickness. Both stiffness and failure load decreased. A shift in cortical parameters was noted in year 2. In the left distal tibia, trabecular volumetric bone mineral density decreased whereas cortical volumetric bone mineral density markedly increased, as did cortical area. There was stability in the trabecular number and thickness. Both stiffness and failure load improved. Findings from HR-pQCT measurements in this patient disclosed that the healing of osteomalacia is not similar across the peripheral skeletal sites in the first years following tumor removal. Results contrasted low but stable volumetric bone mineral density in the distal radius with increase in the distal tibia at the expense of cortical bone. Our report helps further delineate the pattern of bone healing after treatment of this rare bone disorder.

Patients with Crohn's disease are at increased risk for symptomatic nephrolithiasis. Stones in these patients are most commonly composed of calcium oxalate monohydrate or mixed calcium-oxalate and calcium-phosphate. Precipitation of both minerals depends on urinary pH, calcium, phosphate and oxalate excretion. The present manuscript reports on two patients with Crohn's disease and bowel resection, in whom the onset of symptomatic urolithiasis occurred after repeated infusions of ferric carboxymaltose – a drug, which is known to cause hyperphosphaturia. The present study shows that ferric carboxymaltose-induced hyperphosphaturia can be associated with kidney stone formation and symptomatic urolithiasis, especially in patients treated with calcitriol. Calcitriol has been shown to mitigate ferric carboxymaltose-induced secondary hyperparathyroidism and hyperphosphaturia, but is known to increase urinary calcium excretion. Chemical analysis of recovered stones revealed that they were mixed calcium oxalate and phosphate stones. Ring-like deposition of iron detected by spatially resolved elemental analysis using laser ablation-inductively coupled plasma mass spectrometry, showed that the stones also contained iron. Based on our findings, we propose that patients with inflammatory bowel disease requiring intravenous iron therapy should be carefully monitored for the development of hypophosphatemia and urolithiasis. If hypophosphatemia occurs in such patients, calcitriol should be used with caution.

Intravenous iron replacement therapy is a common treatment for iron deficiency. Commonly used agents in this treatment include ferric carboxymaltose, ferric derisomaltose, and saccharated ferric oxide (SFO). These drugs are known to elevate fibroblast growth factor 23 levels, resulting in hypophosphatemia, but in past reports, hypophosphatemia attributable to SFO treatment has been associated mainly with prolonged administration over several weeks. The present study details our experience of a case of moderate hypophosphatemia (<2 mg/dL) in a 22-year-old woman who had no specific history of hypophosphatemia during the first 5 days of SFO treatment, and showed an increase in intact fibroblast growth factor 23 levels within the first week of treatment. Cases of hypophosphatemia have been reported as occurring as early as 1 week after the start of SFO administration in the Japanese Adverse Drug Event Report database. These cases, along with our case, underline the need for awareness of the possibility of hypophosphatemia from the early stage of SFO administration, regardless of the patient's age or dosage, as well as the need to monitor patients to prevent complications.