Hormonal Control of Bone Architecture Throughout the Lifespan: Implications for Fracture Prediction and Prevention.

Background: Skeletal modeling in childhood and adolescence and continuous remodeling throughout the lifespan are designed to adapt to a changing environment and resist external forces and fractures. The flux of sex steroids in men and women, beginning from fetal development and evolving through infancy, childhood, puberty, young adulthood, peri/menopause transition, and postmenopause, is critical for bone size, peak bone mass, and fracture resistance.

Objective: This review will highlight how changes in sex steroids throughout the lifespan affect bone cells and the consequence of these changes on bone architecture and strength.

Structural differences contributing to sex-specific associations between FN BMD and whole-bone strength for adult White women and men.

Hip areal BMD (aBMD) is widely used to identify individuals with increased fracture risk. Low aBMD indicates low strength, but this association differs by sex with men showing greater strength for a given aBMD than women. To better understand the structural basis giving rise to this sex-specific discrepancy, cadaveric proximal femurs from White female and male donors were imaged using nano-CT and loaded in a sideways fall configuration to assess strength.

A skeleton in a huff: insights in etiologies of osteosclerosis.

A 30-yr-old man developed right lower leg pain and a palpable solid mass. Radiographic imaging revealed a periosteal reaction with an exostotic mass arising from the right distal fibula. Generalized skeletal osteosclerosis with periosteal reaction was discovered on a radiographic skeletal survey.

Perspective: A multi-trait integrative approach to understanding the structural basis of bone fragility for pediatric conditions associated with abnormal bone development.

Bone development is a highly orchestrated process that establishes the structural basis of bone strength during growth and functionality across the lifespan. This developmental process is generally robust in establishing mechanical function, being adaptable to many genetic and environmental factors. However, not all factors can be fully accommodated, leading to abnormal bone development and lower bone strength.

Associations Among Hip Structure, Bone Mineral Density, and Strength Vary With External Bone Size in White Women.

Bone mineral density (BMD) is heavily relied upon to reflect structural changes affecting hip strength and fracture risk. Strong correlations between BMD and strength are needed to provide confidence that structural changes are reflected in BMD and, in turn, strength. This study investigated how variation in bone structure gives rise to variation in BMD and strength and tested whether these associations differ with external bone size.

Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline.

Background: Hypercalcemia of malignancy (HCM) is the most common metabolic complication of malignancies, but its incidence may be declining due to potent chemotherapeutic agents. The high mortality associated with HCM has declined markedly due to the introduction of increasingly effective chemotherapeutic drugs. Despite the widespread availability of efficacious medications to treat HCM, evidence-based recommendations to manage this debilitating condition are lacking.

Five-year risk of fracture and subsequent fractures among adults with cerebral palsy.

Background: Epidemiologic evidence documenting the incidence of fracture and subsequent fractures among adults with cerebral palsy (CP) is lacking, which could inform fracture prevention efforts. The objective was to characterize the 5-year rate of initial and subsequent fragility fractures among adults with CP.

Methods: This retrospective cohort study used Medicare claims from 01/01/2008-12/31/2019 from adults ≥18 years old with CP ( = 44,239) and elderly ≥65 years old without CP ( = 2,176,463) as a comparison.

Differential immune landscapes in appendicular versus axial skeleton.

Roughly 400,000 people in the U.S. are living with bone metastases, the vast majority occurring in the spine.

Ca-independent phospholipase Aβ-derived PGE contributes to osteogenesis.

Bone modeling can be modulated by lipid signals such as arachidonic acid (AA) and its cyclooxygenase 2 (COX2) metabolite, prostaglandin E (PGE), which are recognized mediators of optimal bone formation. Hydrolysis of AA from membrane glycerophospholipids is catalyzed by phospholipases A (PLAs). We reported that mice deficient in the Ca- independent PLAbeta (iPLAβ), encoded by Pla2g6, exhibit a low bone phenotype, but the cause for this remains to be identified.

Clinical bone health among adults with cerebral palsy: moving beyond assessing bone mineral density alone.

Aim: To understand associations among bone mineral density (BMD), bone mineral content (BMC), and bone area, and their association with fractures in adults with cerebral palsy (CP).

Method: This retrospective cohort study included 78 adults with CP with a hip dual energy X-ray absorptiometry (DXA) from 1st December 2012 to 3rd May 2021 performed at the University of Michigan. Data-driven logistic regression techniques identified which, if any, DXA-derived bone traits (e.

Osteoblasts Generate Testosterone From DHEA and Activate Androgen Signaling in Prostate Cancer Cells.

Bone metastasis is a complication of prostate cancer in up to 90% of men afflicted with advanced disease. Therapies that reduce androgen exposure remain at the forefront of treatment. However, most prostate cancers transition to a state whereby reducing testicular androgen action becomes ineffective.

Dura promotes metastatic potential in prostate cancer through the CXCR2 pathway.

Purpose: Spinal metastases are common in cancer. This preferential migration/growth in the spine is not fully understood. Dura has been shown to affect the surrounding microenvironment and promote cancer growth.

Adrenal metastasis as the initial diagnosis of synchronous papillary and follicular thyroid cancer.

Background: Differentiated thyroid cancer uncommonly presents with distant metastases. Adrenal metastasis from differentiated thyroid cancer presenting as the initial finding is even less common.

Case Presentation: A 71-year-old male was incidentally found on chest CT to have bilateral thyroid nodules, which were confirmed on ultrasound.

Outcome of Clinical Genetic Testing in Patients with Features Suggestive for Hereditary Predisposition to PTH-Mediated Hypercalcemia.

Primary hyperparathyroidism (pHPT) is associated with familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), 2A (MEN2A), MEN-like syndromes (CDKN1B), and CDC73-related disorder (hyperparathyroidism - jaw tumor syndrome (HPJT)). Familial hypocalciuric hypercalcemia (FHH) caused by CASR variants is an important differential diagnosis for pHPT. In order to evaluate the contribution of hereditary causes to pHPT in patients encountered in a specialized clinic, we conducted a retrospective study on patients with pHPT that underwent germline genetic testing.

A rare cause of atraumatic fractures: case series of four patients with tumor-induced osteomalacia.

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that presents with hypophosphatemia, bone pain, muscle weakness and fractures. We report a case series of four patients with TIO that resulted in significant muscle weakness and multiple atraumatic fractures.

Case Presentation: Four patients were referred to an endocrinology clinic for the evaluation of multiple atraumatic fractures, muscle weakness, generalized muscle and joint pain.

A case report of T-box 1 mutation causing phenotypic features of chromosome 22q11.2 deletion syndrome.

Background: The heterozygous microdeletion of chromosome 22q11.2 results in a spectrum of disorders, including DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS), with phenotypic features that can include the classic triad of congenital heart disease (CHD), thymic aplasia and hypoparathyroidism. Such microdeletions are usually detectable by fluorescence in situ hybridization (FISH).

Castration Determines the Efficacy of ETAR Blockade in a Mouse Model of Prostate Cancer Bone Metastasis.

Bone metastasis is a painful complication of advanced prostate cancer. Endothelin-1 is a tumor-secreted factor that plays a central role in osteoblast activation and the osteosclerotic response of prostate cancer metastatic to bone. Antagonists that block the activation of the endothelin A receptor (ETAR), located on osteoblasts, reduce osteoblastic bone lesions in animal models of bone metastasis.

The Endothelin-A Receptor Antagonist Zibotentan Induces Damage to the Nasal Olfactory Epithelium Possibly Mediated in Part through Type 2 Innate Lymphoid Cells.

Zibotentan, an endothelin-A receptor antagonist, has been used in the treatment of various cardiovascular disorders and neoplasia. Castrated athymic nude mice receiving zibotentan for a preclinical xenograft efficacy study experienced weight loss, gastrointestinal bloat, and the presence of an audible respiratory click. Human side effects have been reported in the nasal cavity, so we hypothesized that the nasal cavity is a target for toxicity in mice receiving zibotentan.

Association of Vitamin D and Parathyroid Hormone With Barrett's Esophagus.

Background: Esophageal adenocarcinoma has been inversely associated with exposure to ultraviolet radiation. This could be because of vitamin D deficiency or hyperparathyroidism promoting gastroesophageal reflux disease (GERD) and Barrett's esophagus.

Aim: The aim of this study is to determine the association between parathyroid hormone (PTH) and vitamin D deficiency with GERD symptoms, erosive esophagitis, and Barrett's esophagus.

Predominance of Spinal Metastases Involving the Posterior Vertebral Body.

Background: Spinal metastases pose significant morbidity. For many histologies, the spine is a frequent site for bone metastases. This predilection is not fully understood, and there are conflicting reports regarding the distribution within the vertebral body itself.

The challenges of diagnosing osteoporosis and the limitations of currently available tools.

Dual-energy X-ray absorptiometry (DXA) was the first imaging tool widely utilized by clinicians to assess fracture risk, especially in postmenopausal women. The development of DXA nearly coincided with the availability of effective osteoporosis medications. Although osteoporosis in adults is diagnosed based on a T-score equal to or below - 2.

DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis.

Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression.

Dural Cells Release Factors Which Promote Cancer Cell Malignancy and Induce Immunosuppressive Markers in Bone Marrow Myeloid Cells.

Background: Thirty per cent of cancer patients develop spine metastases with a substantial number leading to spinal cord compression and neurological deficits. Many demonstrate a propensity toward metastasis to the posterior third of the vertebral body. The dura, the outer layer of the meninges, lies in intimate contact with the posterior border of the vertebral body and has been shown to influence adjacent bone.

Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research.

Bisphosphonates (BPs) are the most commonly used medications for osteoporosis. This ASBMR report provides guidance on BP therapy duration with a risk-benefit perspective. Two trials provided evidence for long-term BP use.