Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study.

Objectives: As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over.

Methods: A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses.

Consumption of dairy foods to achieve recommended levels for older adults has no deleterious effects on serum lipids.

Background And Aims: Correction of calcium and protein undernutrition using milk, yoghurt, and cheese in older adults in aged care homes is associated with reduced fractures and falls. However, these foods contain potentially atherogenic fats. We aimed to determine whether this intervention that increased dairy consumption to recommended levels adversely affects serum lipid profiles.

Denosumab Prevents Bone Loss and Microarchitectural Deterioration in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression Therapy: A Randomized Controlled Trial.

Purpose: Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)-positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women.

Methods: In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (at 0 and 6 months).

Association of Serum Phosphate, Calcium and Alkaline Phosphatase With Risk of Incident Fractures in Healthy Older Adults.

Context: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodeling.

Objective: We examined the associations between levels of phosphate, calcium (Ca), and alkaline phosphatase (ALP), and fracture risk in initially healthy older individuals.

Methods: A post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16 703 Australian participants aged 70 years and older and 2411 US participants aged 65 years and older.

Cardiometabolic Effects of Denosumab in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression: RCT.

Context: Menopause is associated with changes in musculoskeletal, body composition, and metabolic parameters that may be amplified in premenopausal women receiving estradiol suppression for breast cancer. Denosumab offsets deleterious skeletal effects of estradiol suppression and has been reported to have effects on body composition and metabolic parameters in preclinical and observational studies, but evidence from double-blind randomized controlled trials is limited.

Objective: To assess the effect of denosumab on body composition and metabolic parameters.

Bone Remodeling and Modeling: Cellular Targets for Antiresorptive and Anabolic Treatments, Including Approaches Through the Parathyroid Hormone (PTH)/PTH-Related Protein Pathway.

Bone is continuously in a state of building and renewal, though the process of remodeling that takes place at many sites asynchronously throughout the skeleton, with bone formation and resorption equal at these sites (bone multicellular units). Remodeling takes place on bone surfaces, both on trabeculae and in the cortex, and serves the purposes of replacing old bone or that damaged by microfractures throughout the skeleton. The bone loss and consequent osteoporotic fractures that result from excess resorption over formation have mainly been prevented or treated by antiresorptive drugs that inhibit osteoclast formation and/or activity.

Reducing hip and non-vertebral fractures in institutionalised older adults by restoring inadequate intakes of protein and calcium is cost-saving.

Background: older adults in aged care account for 30% of the population burden of hip fractures. Nutritional interventions to correct under nutrition reduce these debilitating fractures, perhaps partly by reducing falls and slowing deterioration in bone morphology.

Objective: to determine whether a nutritional approach to fracture risk reduction in aged care homes is cost-effective.

A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients.

Unlabelled: Low serum alkaline phosphatase (ALP) was found in 9% of patients attending an osteoporosis clinic, 0.6% of hospital patients, and 2/22 with an atypical femoral fracture. Hypophosphatasia was diagnosed in 3% of osteoporosis clinic patients with low ALP.

Daily Low-Dose Aspirin and Risk of Serious Falls and Fractures in Healthy Older People: A Substudy of the ASPREE Randomized Clinical Trial.

Importance: Falls and fractures are frequent and deleterious to the health of older people. Aspirin has been reported to reduce bone fragility and slow bone loss.

Objective: To determine if daily low-dose aspirin (100 mg) reduces the risk of fractures or serious falls (fall-related hospital presentations) in healthy older men and women.

Bone microarchitecture and estimated failure load are deteriorated whether patients with chronic kidney disease have normal bone mineral density, osteopenia or osteoporosis.

Introduction: Measurement of bone mineral density (BMD) is recommended in patients with chronic kidney disease (CKD). However, most persons in the community and most patients with CKD have osteopenia, suggesting fracture risk is low. Bone loss compromises bone microarchitecture which increases fragility disproportionate to modest deficits in BMD.

The effect of denosumab and alendronate on trabecular plate and rod microstructure at the distal tibia and radius: A post-hoc HR-pQCT study.

Background: Age-related trabecular microstructural deterioration and conversion from plate-like trabeculae to rod-like trabeculae occur because of unbalanced rapid remodeling. As denosumab achieves greater remodeling suppression and lower cortical porosity than alendronate, we hypothesized that denosumab might also preserve trabecular plate microstructure, bone stiffness and strength more effectively than alendronate.

Methods: In this post hoc analysis of a phase 2 study, postmenopausal women randomized to placebo (P, n = 74), denosumab (D, n = 72), or alendronate (A, n = 68).

Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia.

Summary: Hypophosphatasia (HPP) is a rare and under-recognised genetic defect in bone mineralisation. Patients presenting with fragility fractures may be mistakenly diagnosed as having osteoporosis and prescribed antiresorptive therapy, a treatment which may increase fracture risk. Adult-onset HPPhypophosphatasia was identified in a 40-year-old woman who presented with bilateral atypical femoral fractures after 4 years of denosumab therapy.

Recovery of quality of life is associated with lower mortality 5-year post-fracture: the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS).

Unlabelled: Little is known about factors that lead to excess mortality post-fracture. This study demonstrated that 5-year mortality is lower in older adults who recovered to their pre-fracture health-related quality of life (HRQoL) at 12-months compared to those who did not recover. Our results highlight the importance of post-fracture interventions known to improve HRQoL.

High Cortico-Trabecular Transitional Zone Porosity and Reduced Trabecular Density in Men and Women with Stress Fractures.

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.

Physiological and Pharmacological Roles of PTH and PTHrP in Bone Using Their Shared Receptor, PTH1R.

Parathyroid hormone (PTH) and the paracrine factor, PTH-related protein (PTHrP), have preserved in evolution sufficient identities in their amino-terminal domains to share equivalent actions upon a common G protein-coupled receptor, PTH1R, that predominantly uses the cyclic adenosine monophosphate-protein kinase A signaling pathway. Such a relationship between a hormone and local factor poses questions about how their common receptor mediates pharmacological and physiological actions of the two. Mouse genetic studies show that PTHrP is essential for endochondral bone lengthening in the fetus and is essential for bone remodeling.

Heterogeneity in microstructural deterioration following spinal cord injury.

Background: Modelling and remodelling adapt bone morphology to accommodate strains commonly encountered during loading. If strains exceed a threshold threatening fracture, modelling-based bone formation increases bone volume reducing these strains. If unloading reduces strains below a threshold that inhibits resorption, increased remodelling-based bone resorption reduces bone volume restoring strains, but at the price of compromised bone volume and microstructure.

Cost-effectiveness of treatment of women aged 70 years and older with both osteopenia and microstructural deterioration.

Objective: Treatment is usually withheld from women with osteopenia even though they are the source of over 70% of all women having fragility fractures. As microstructural deterioration increases fracture risk and zoledronate reduces it, we aimed to determine whether identifying and treating women with osteopenia and severe microstructural deterioration is cost-effective. We also compared the health economic outcomes of 'global' versus 'targeted' treatment using SFS of women aged ≥70 years with osteopenia.

Differing Effects of Zoledronic Acid on Bone Microarchitecture and Bone Mineral Density in Men Receiving Androgen Deprivation Therapy: A Randomized Controlled Trial.

Androgen deprivation therapy (ADT) given to men with prostate cancer causes rapid and severe sex steroid deficiency, leading to increased bone remodeling and accelerated bone loss. To examine the effects of a single dose of zoledronic acid on bone microarchitecture, we conducted a 2-year randomized placebo controlled trial in 76 men, mean age (interquartile range [IQR]) 67.8 years (63.

Reduced Bone Modeling and Unbalanced Bone Remodeling: Targets for Antiresorptive and Anabolic Therapy.

Bone loss during advancing age is the net result of reduced modeling-based bone formation upon the outer (periosteal) envelope and unbalanced remodeling by basic multicellular units (BMUs) upon the three (intracortical, endocortical, and trabecular) components of the inner (endosteal) bone envelope. Each BMU deposits less bone than resorbed, reducing total bone volume and deteriorating the microstructure of the diminished residual bone volume.Antiresorptive agents like bisphosphonates reduce, but do not abolish, the rate of bone remodeling - fewer BMUs remodel, "turn over," the volume of bone.

Aspirin and fracture risk: a systematic review and exploratory meta-analysis of observational studies.

Objectives: This review provides insights into the potential for aspirin to preserve bone mineral density (BMD) and reduce fracture risk, building knowledge of the risk-benefit profile of aspirin.

Methods: We conducted a systematic review and exploratory meta-analysis of observational studies. Electronic searches of MEDLINE and Embase, and a manual search of bibliographies was undertaken for studies published to 28 March 2018.

Deterioration of Cortical and Trabecular Microstructure Identifies Women With Osteopenia or Normal Bone Mineral Density at Imminent and Long-Term Risk for Fragility Fracture: A Prospective Study.

More than 70% of women sustaining fractures have osteopenia or "normal" bone mineral density (BMD). These women remain undetected using the BMD threshold of -2.5 SD for osteoporosis.

Osteocalcin and its forms across the lifespan in adult men.

Purpose: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease.