David A Hanley

University of Calgary · Department of Medicine

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We...

Fracture risk increases with lower areal BMD (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) DXA which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measur...

In a 36 month RCT examining the effect of high dose vitamin D3 on radial and tibial total bone mineral density (TtBMD), measured by high resolution peripheral quantitative tomography (HR-pQCT), participants (311 healthy males and females aged 55-70 years with DXA T-scores > -2.5, without vitamin D deficiency) were randomized to receive 400 IU (N =...

Most fracture risk assessment tools use clinical risk factors combined with bone mineral density (BMD) to improve assessment of osteoporosis; however, stratifying fracture risk remains challenging. This study developed a fracture risk assessment tool that uses information about volumetric bone density and three-dimensional structure, obtained using...

Femoral neck areal bone mineral density (FN aBMD) is a key determinant of fracture risk in older adults, however the majority of individuals who have a hip fracture are not considered osteoporotic according to their FN aBMD. This study uses novel tools to investigate the characteristics of bone microarchitecture that underpin bone fragility. Recent...

Reducing fracture risk is the objective of osteoporosis treatment. Bone-forming osteoporosis drugs increase bone mass, restore bone microarchitecture, and reduce fracture risk more effectively than oral bisphosphonates, providing strong justification for the use of these agents as the initial therapy or after anti-remodeling agents in patients at v...

ABSTRACT High‐dose vitamin D supplementation (4000 or 10,000 IU/d) in vitamin D‐sufficient individuals results in a dose‐dependent decrease in radius and tibia total bone mineral density (Tt.BMD) compared with 400 IU/d. This exploratory analysis examined whether the response to high‐dose vitamin D supplementation depends on imaging modality and ske...

ABSTRACT Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss; and (ii) clinically...

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a "one-size-fits-all" approach to diagnosis and management of osteoporosis may not b...

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analysed the data from a study collecting lumbar CT...

Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss; and (ii) clinically significa...

We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D image registration to account for misalignment between images. This reduced variability in longitudinal FE estimates and improved our ability to measure in vivo changes in HR-pQCT studies...

Study Purpose Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing...

Fracture determinants differ between Canadians of Chinese and White descent, the former constituting the second largest visible minority group in Canada. The results of this study support the importance of characterizing bone health predictors in Canadians of different ethnicity to improve population-specific fracture prevention and treatment strat...

Three years of high‐dose vitamin D supplementation (400, 4000, 10,000 IU) in healthy vitamin D‐sufficient individuals aged 55‐70 years (serum 25(OH)D 30‐125 nmol/L at baseline), resulted in a negative dose‐response relationship for bone density and strength. This study examined whether response differed between males and females. 311 participants (...

Although high-dose vitamin D supplementation is common, effects on arterial calcification remain unexplored. Tibial artery calcification was identified and quantified over 3 years in participants randomized to 400, 4000, or 10,000 IU vitamin D3 daily. High-dose vitamin D supplementation did not affect the development or progression of arterial calc...

There are currently no population‐based reference datasets available for volumetric bone mineral density and microarchitecture parameters measured using the second‐generation HR‐pQCT, yet the technology is rapidly becoming a standard for studies of bone microarchitecture. Although cross‐calibrated datasets from the first‐generation HR‐pQCT have bee...

Existing fracture risk assessment tools are not designed to predict fracture‐associated consequences, possibly contributing to the current under‐management of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and consequences. The study involved 8965 people aged ≥60 y...

Longitudinal studies of bone using high-resolution medical imaging may result in non-physiological measurements of longitudinal changes. In this study, we determined that three-dimensional image processing techniques best capture realistic longitudinal changes in bone density and should therefore be used with high-resolution imaging when studying b...

This study aimed to evaluate associations of parity and breastfeeding history with postmenopausal bone loss. Early postmenopausal women from the Canadian Multicentre Osteoporosis Study were divided into three groups based on their reproductive histories: nulliparous (NP, n = 10), parous with < 6 months breastfeeding (P-NBF, n = 14), and parous with...

Vitamin D supplementation is proposed as a fall prevention strategy, as it may improve neuromuscular function. We examined whether three years of vitamin D supplementation (400, 4000 or 10,000 IU daily) affects postural sway in older adults. Three hundred and seventy-three non-osteoporotic, vitamin D-sufficient, community-dwelling healthy adults, a...

We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk th...

In Reply Drs Lippi and Targher, as well as Dr Li and colleagues, comment that the findings of our trial are applicable to a specific study population. Although Lippi and Targher’s thresholds for 25(OH)D deficiency and insufficiency are above those of Health Canada and the Institute of Medicine (IOM),¹ we share their concern that our results might b...

Using data from the Canadian Multicentre Osteoporosis Study, several risk factors predictive of imminent (2-year) risk of low-trauma non-vertebral fracture among high-risk women were identified, including history of falls, history of low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to targeting...

Context Over 3% of adults report vitamin D intakes ≥4000 IU/day, but the safety of this practice is unknown. Objective To establish whether vitamin D doses up to 10000 IU/day are safe and well-tolerated. Design The Calgary Vitamin D Study was a three-year double-blind RCT. Setting Single-centre study at the University of Calgary, Canada. Partic...

Introduction: Five-year changes in multisite quantitative ultrasound-assessed speed of sound (SOS in m/s) were studied in a cohort of women and men. The impacts of antiresorptive therapies and menopausal status on SOS were also assessed. Methodology: Two SOS assessments, clinical assessments, and comprehensive questionnaires were completed 5 yea...

Importance Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day. Objective To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength....

Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates an...

Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. Introduct...

Patients often start treatment to reduce fracture risk because of a bone mineral density T-score consistent with osteoporosis (≤ -2.5). Others with a T-score above -2.5 may be treated when there is a history of fragility fracture or when a fracture risk algorithm categorizes them as having a high risk for fracture. It is common to initiate therapy...

Although the short‐term impact of incident fragility fractures on health‐related quality of life (HRQL) of older people has been confirmed, we lack long‐term evidence. We explored the impact of incident fragility fractures on HRQL, among people aged 50 years and older, using 10‐year prospective data from the Canadian Multicentre Osteoporosis Study...

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. Introduction Emerging evidence sug...

Background: Although areal bone mineral density (aBMD) assessed by dual-energy x-ray absorptiometry (DXA) is the clinical standard for determining fracture risk, most older adults who sustain a fracture have T scores greater than -2·5 and thus do not meet the clinical criteria for osteoporosis. Importantly, bone fragility is due to low BMD and det...

Introduction Speed of sound (SOS in m/s) measured with the BeamMed Sunlight Multi-site quantitative ultrasound (QUS) can predict fracture in women over a five-year period, independent of bone mineral density and other significant risk factors for fracture. The rate of SOS decline may better identify patients with an elevated risk for fracture than...

Objectives: To assess combined hormonal contraceptives (CHC) use and adolescent women's peak areal bone mineral density (BMD) accrual. Methods: We enrolled 527 randomly selected women across Canada (2004-6) divided by age into adolescents (16-19) and young adults (20-24) and by CHC use to ever (E-CHC)/never (N-CHC) users. At baseline and year 2...

Dear Dr. Civitelli, In discussing such advances, they include spinal morphometry, and specifically refer to and illustrate the Genant semi‐quantitative (GSQ) paradigm,² although also referring to the algorithm‐based qualitative (ABQ) method³ of vertebral evaluation in the diagnosis of osteoporotic vertebral fractures (OVF). Although in its day the...

The optimum dose of vitamin D and corresponding serum 25-hydroxyvitamin D (25OHD) concentration for bone health is still debated and some health practitioners are recommending doses well above the Canada/USA recommended Dietary Reference Intake (DRI). We designed a three-year randomized double-blind clinical trial investigating whether there are do...

The aim of this prospective study was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) to determine if baseline skeletal parameters can predict incident fragility fracture in women and, secondly, to establish if women that fracture lose bone at a faster rate than those who do not fracture. Women older than 60 years who e...

We compared two methods for osteoporotic vertebral fracture (VF) assessment on lateral spine radiographs, the Genant semi-quantitative (GSQ) technique and a modified algorithm-based qualitative (mABQ) approach. We evaluated 4465 women and 1771 men > 50 years old from the Canadian Multicentre Osteoporosis Study with available X-ray images at baselin...

Osteoporosis is a chronic disease that requires life-long strategies to reduce fracture risk. Few trials have investigated the balance of benefits and risk with long-term use of osteoporosis therapies and fewer still have investigated the consequences of treatment discontinuation. The best available evidence suggests that up to 10 years of treatmen...

Longitudinal studies assessing age-related changes using high-resolution peripheral quantitative computed tomography (HR-pQCT) provide novel insight compared with cross-sectional analyses. The purpose of this cohort study was 1) to determine individuals' change in HR-pQCT parameters over five years relative to least significant change (LSC), and 2)...

Introduction: After fragility fracture, <20% of patients receive osteoporosis treatment. FLS are recommended to address this deficit but there are very few economic analyses of different FLS models. Therefore, we conducted an economic analysis of a 1i (=type C) FLS called "Catch a Break (CaB)." Methods: CaB is a population-based FLS in Alberta,...

Data on long-term consequences of non-hip non-vertebral (NHNV) fractures, accounting for approximately two thirds of all fragility fractures are scanty. Our study aimed to quantify the population-wide impact of NHNV fractures on mortality. The national population-based prospective cohort study (Canadian Multicentre Osteoporosis Study) included 5526...

Objective: Vitamin D is important in promoting healthy pregnancy and fetal development. We undertook this study to measure 25-hydroxyvitamin D in maternal and cord blood and to identify maternal factors related to vitamin D status in Calgary. Methods: Blood samples collected at the time of delivery from the Alberta Pregnancy Outcomes and Nutriti...

Introduction: The purpose of this study was to compare changes in bone density and microarchitecture in peri- and post-menopausal women over 6 years. Methods: Peri- (n = 26) and post- (n = 65) menopausal women were selected from the Canadian Multicenter Osteoporosis Study. Caucasian women were scanned on dual x-ray absorptiometry (DXA) and high-...

Trabecular bone score (TBS) is a gray-level texture measure derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images that predicts fractures independent of bone mineral density (BMD). Increased abdominal soft tissue in individuals with elevated body mass index (BMI) absorbs more X-rays during image acquisition for BMD measurement and...

Nitrates may have beneficial effects on bone. To determine if nitrates were associated with increased bone mineral density (BMD), we conducted a secondary analysis using data from subjects in a prospective study. Subjects reporting nitrate use had increased BMD compared with non-users, confirming that nitrates have positive BMD effects in women and...

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-bas...

End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine...

The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to fo...

Objectives: To determine seasonal variations in the vitamin D status of Saudi adolescent girls in Riyadh, Kingdom of Saudi Arabia (KSA) and its effect in biochemical and clinical characteristics. Methods: In this prospective study, a total of 2000 Saudi females aged 12-18 years from different schools in Riyadh, KSA participated and submitted a gen...

Background: The aims of this study were to determine if pregnant women consumed the recommended vitamin D through diet alone or through diet and supplements, and if they achieved the current reference range vitamin D status when their reported dietary intake met the current recommendations. Methods: Data and banked blood samples collected in sec...

The purpose of this study was to develop age-, site- and sex-specific centile curves for common high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element (FE) parameters for males and females over the age of 16 years. Participants (N = 866) from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos)...

Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary SHOTZ study. Patients were eligible to enter a 12-month extension on th...

Women with Turner syndrome (TS) are known to be at risk of osteoporosis. While childhood growth hormone (GH) treatment is common in TS, the impact of this therapy on bone health has been poorly understood. The objective of this study was to determine the influence of childhood GH treatment on adult bone quality in women with TS. 28 women aged 17-45...

Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of...

We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns [Prudent (fruit, vegetables, whole grains, fish, and legumes) and Western (soft drinks, potato chips, French fries, meats, and desserts)] from a semi-quantitative...

Background: Vitamin D is critical for healthy pregnancies and normal fetal development. It is important to accurately ascertain vitamin D status in mothers and their newborns to establish the optimal vitamin D concentration during pregnancy. There are many different metabolites and epimers of vitamin D in peripheral blood and controversy as to the...

Vertebral fractures are common and can result in acute and chronic pain, decreases in quality of life and diminished lifespan. The identification of vertebral fractures is important as they are robust predictors of future fractures. The majority of vertebral fractures do not come to clinical attention. Numerous modalities exist for visualizing susp...

High dietary protein has been hypothesized to cause lower bone mineral density (BMD) and greater fracture risk. Previous results are conflicting and few studies have assessed potential differences related to differing protein sources. Participants/Measures Protein intake was assessed as percent of total energy intake (TEI) at Year 2 (1997-99) using...

Vitamin D deficiency is a cardiovascular risk factor.1,2 Deficiency in both 25-hydroxy vitamin D, the barometer of vitamin D status, and the more biologically active 1,25-dihydroxy vitamin D is associated with increased risk of sudden cardiac death (SCD),2–4 particularly in the chronic kidney disease (CKD) population.3,4 Studies have suggested that...

Dual-energy X-ray absorptiometry (DXA) is an important tool for the estimate of fracture risk through the measurement of bone mineral density (BMD). Similarly, multisite quantitate ultrasound can prospectively predict future fracture through the measurement of speed of sound (SOS). This investigation compared BMD (at the femoral neck, total hip, an...

Unlabelled: The relation between serum 25-hydroxy vitamin D [25(OH)D] and bone quality is not well understood, particularly for high levels. We measured bone microarchitecture in three groups of people stratified by their serum 25(OH)D. There was a weak association of serum 25(OH)D and microarchitecture for this cross-sectional population, suggest...

Studies assessing bone health often select the dominant or nondominant limb to scan, but not both, for efficiency reasons. New scanning technology allows 3-dimensional (3D) visualization of the microarchitecture in bone, but it is not well understood whether there are differences between the dominant and nondominant limbs. Using 3D high-resolution...

James Bertram Collip made major contributions to the emerging field of endocrinology in the first half of the twentieth century. While on sabbatical leave from the University of Alberta, he was a major contributor to the discovery of insulin at the University of Toronto. His development of a methodology for extracting the active insulin from pancre...

Cardiovascular disease (CVD) and vitamin D deficiency are extremely prevalent worldwide (Holick 2007; World Health Organization 2011). The potential link between vitamin D deficiency and CVD‐related death in both healthy and diseased populations is a growing area of translational research. Historically, the traditional role of vitamin D in maintain...

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme acid beta-glucosidase (glucocerebrosidase) due to mutations in the GBA gene. The most common form (type I) is associated with severe hematologic, visceral and bone disease. Disease-modifying treatments, such as enzyme replacement therapy and subs...