91220799 The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: A randomized study comparing intermittent treatment and an ADFR regime

Identifying vertebral fractures is prudent in the management of osteoporosis and the current literature suggests that less than one-third of incidental vertebral fractures are reported. The aim of this study is to determine the prevalence of reported and unreported vertebral fractures in computerized tomography pulmonary angiograms (CTPA) and their relevance to clinical outcomes. All acutely unwell patients aged 75 or older who underwent CTPAs were reviewed retrospectively. 179 CTPAs were reviewed to identify any unreported vertebral fractures. A total of 161 were included for further analysis. Of which, 14.3% (23/161) were reported to have a vertebral fracture, however, only 8.7% (14/161) of reports used the correct terminology of ‘fracture’. On subsequent review, an additional 19.3% (31/161) were noted to have vertebral fractures. Therefore, the overall prevalence of vertebral fractures was 33.5% (54/161). A total of 22.2% (12/54) of patients with a vertebral fracture on CTPA sustained a new fragility fracture during the follow-up period (4.5 years). In comparison, a significantly lower 10.3% (11/107) of patients without a vertebral fracture developed a subsequent fragility fracture during the same period (p = 0.04). Overall mortality during the follow-up period was significantly higher for patients with vertebral fractures (68.5%, 37/54) as compared to those without (45.8%, 49/107, p = 0.006). Vertebral fractures within the elderly population are underreported on CTPAs. The significance of detecting incidental vertebral fractures is clear given the increased rates of subsequent fractures and mortality. Radiologists and physicians alike must be made aware of the importance of identifying and treating incidental, vertebral fragility fractures.

https://www.mdpi.com/2308-3417/5/3/56/pdf

Prevalence of Vertebral Fractures in CTPA’s in Adults Aged 75 and Older and Their Association with Subsequent Fractures and Mortality

Since phosphorus is a component of hydroxyapatite, its prolonged deprivation affects bone mineralization. Fibroblast growth factor 23 (FGF23) is essential for maintaining phosphate homeostasis and is mainly produced by osteocytes. FGF23 increases the excretion of inorganic phosphate (Pi) and decreases the production of 1,25-dihydroxyvitamin D in the kidneys. Osteocytes are cells of osteoblastic lineage that have undergone terminal differentiation and become embedded in mineralized bone matrix. Osteocytes express FGF23 and other multiple genes responsible for hereditary hypophosphatemic rickets, which include phosphate-regulating gene homologous to endopeptidase on X chromosome (PHEX), dentin matrix protein 1 (DMP1), and family with sequence similarity 20, member C (FAM20C). Since inactivating mutations in PHEX, DMP1, and FAM20C boost the production of FGF23, these molecules might be considered as local negative regulators of FGF23. Mouse studies have suggested that enhanced FGF receptor (FGFR) signaling is involved in the overproduction of FGF23 in PHEX-deficient X-linked hypophosphatemic rickets (XLH) and DMP1-deficient autosomal recessive hypophosphatemic rickets type 1. Since FGFR is involved in the transduction of signals evoked by extracellular Pi, Pi sensing in osteocytes may be abnormal in these diseases. Serum levels of sclerostin, an inhibitor Wnt/β-catenin signaling secreted by osteocytes, are increased in XLH patients, and mouse studies have suggested the potential of inhibiting sclerostin as a new therapeutic option for the disease. The elucidation of complex abnormalities in the osteocytes of FGF23-related hypophosphatemic diseases will provide a more detailed understanding of their pathogenesis and more effective treatments.

/pdf/osteocytes-and-the-pathogenesis-of-hypophosphatemic-rickets-3b8czzbb.pdf

Osteocytes and the pathogenesis of hypophosphatemic rickets

Osseointegration of porous titanium and tantalum implants in ovariectomized rabbits: A biomechanical study

Osseointegration of porous titanium and tantalum implants in ovariectomized rabbits: A biomechanical study.

Early research has suggested a rather straightforward relation between phosphate exposure, increased serum FGF23 (Fibroblast Growth Factor 23) concentrations and clinical endpoints. Unsurprisingly, however, subsequent studies have revealed a much more complex interplay between autocrine and paracrine factors locally in bone like PHEX and DMP1, concentrations of minerals in particular calcium and phosphate, calciprotein particles, and endocrine systems like parathyroid hormone PTH and the vitamin D system. In addition to these physiological regulators, an expanding list of disease states are shown to influence FGF23 levels, usually increasing it, and as such increase the burden of disease. While some of these physiological or pathological factors, like inflammatory cytokines, may partially confound the association of FGF23 and clinical endpoints, others are in the same causal path, are targetable and hence hold the promise of future treatment options to alleviate FGF23-driven toxicity, for instance in chronic kidney disease, the FGF23-associated disease with the highest prevalence by far. These factors will be reviewed here and their relative importance described, thereby possibly opening potential means for future therapeutic strategies.

/pdf/shedding-light-on-the-complex-regulation-of-fgf23-3soi0p5w.pdf

Shedding Light on the Complex Regulation of FGF23

The purpose of this review is to critically evaluate the current literature regarding implant fixation in osteoporotic bone. Clinical studies have not only demonstrated the growing prevalence of osteoporosis in patients undergoing total joint replacement (TJR) but may also indicate a significant gap in screening and treatment of this comorbidity. Osteoporosis negatively impacts bone in multiple ways beyond the mere loss of bone mass, including compromising skeletal regenerative capacity, architectural deterioration, and bone matrix quality, all of which could diminish implant fixation. Recent findings both in preclinical animal models and in clinical studies indicate encouraging results for the use of osteoporosis drugs to promote implant fixation. Implant fixation in osteoporotic bone presents an increasing clinical challenge that may be benefitted by increased screening and usage of osteoporosis drugs.

Biomechanics of Implant Fixation in Osteoporotic Bone

Sclerostin antibody improves phosphate metabolism hormones, bone formation rates, and bone mass in adult Hyp mice.

To test how osteoporosis drugs affect bone matrix maturation during cortical bone remodeling, 72 pregnant rats were switched from a 0.4% to a 0.01% calcium diet at parturition for a 23-day lactation period. At weaning, eight dams were sacrificed to establish baseline values, while the remaining dams were returned to 0.4% calcium and treated with vehicle (saline), sodium fluoride (NaF), zoledronic acid (ZA), or sclerostin antibody (Scl-Ab) for either 7 or 28 days (eight animals per group per time point). Femora were examined by μCT, dynamic histomorphometry, Fourier transform infrared imaging, and three-point bending of notched specimens. Cortical porosity decreased in all groups from baseline to day 28. Intracortical mineralizing surface (MS/BS) and mineral apposition rate (MAR), as well as the mineral-to-matrix ratio were unaffected by treatment, but intracortical crystallinity was increased in the ZA group at day 10 compared with vehicle. Cortical area increased in all groups over 28 days mainly because of an addition of bone at the endocortical surface. Endocortical MS/BS did not vary among the groups, but endocortical MAR was suppressed in the NaF group at day 2 and elevated in the Scl-Ab group at day 4 compared with vehicle. Endocortical mineral-to-matrix ratio was increased at days 5 and 10 following NaF treatment and endocortical crystallinity was increased at day 5 following ZA treatment compared with vehicle. Fracture toughness did not differ among the groups. Thus, the treatments affected matrix maturation more strongly at the endocortical then intracortical envelope. In this model of induced remodeling, the bone formation phase is synchronized at multiple sites, facilitating study of the effects of drugs or other bone-targeting agents on matrix maturation independent of their effects on the initiation of remodeling. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1002/jbm4.10344

Kyle D. Anderson

Papers

Biomechanics of Implant Fixation in Osteoporotic Bone

Sclerostin antibody improves phosphate metabolism hormones, bone formation rates, and bone mass in adult Hyp mice.

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling.

The relative contribution of bone microarchitecture and matrix composition to implant fixation strength in rats.