As part of the celebrations for the 150th anniversary of the Hospital for Special Surgery, Prof. Donnelly presented a talk entitled, “Collagen as a Determinant of Bone Properties” at the Adele L. Boskey, Ph.D. Symposium on Mineralized Tissues. The symposium honored Dr. Boskey’s 40-year career devoted to investigation of the mechanism of biologic mineralization, as well as to mentoring young investigators.
Chin wins ELI Undergraduate Research Award
Michelle Chin was awarded an Engineering Learning Initiatives Undergraduate Research Award for her proposal entitled, “Effect of bisphosphonates on bone tissue composition in postmenopausal women with fragility fractures.” The ELI grant will support her work in the lab this summer. Congratulations Michelle!
Lloyd awarded NSF Graduate Research Fellowship
PhD student Ashley Lloyd was awarded a National Science Foundation Graduate Research Fellowship. NSF received over 13,000 applications for the 2013 competition and made 2,000 award offers. Congratulations Ashley!
Donnelly awarded NIH career development grant
Despite having higher than average bone density, patients with type 2 diabetes paradoxically have increased risk of fracture relative to individuals without diabetes. NIH/NIAMS has awarded Prof. Donnelly a career development grant to investigate the changes in collagen properties that occur in bone tissue with type 2 diabetes and their relationship to fracture risk. Key collaborators include Prof. Deepak Vashishth at Rensselaer Polytechnic Institute and Dr. Joseph Lane at the Hospital for Special Surgery.
Donnelly E, Saleh A, Unnanuntana A, Lane JM. Atypical femoral fractures: epidemiology, etiology, and patient management. Curr Opin Support Palliat Care. 2012.
Abstract
Purpose of review: To review the definition, epidemiology, and putative pathophysiology of atypical femoral fractures and propose strategies for the management of patients with atypical fractures as well as patients on long-term bisphosphonates without atypical fractures.
Recent findings: Recent epidemiologic evidence shows that the absolute incidence of atypical femoral fractures is small compared with the incidence of typical hip fractures. However, long-term bisphosphonate use may be an important risk factor for atypical fractures, and minimal additional antifracture benefit has been demonstrated for treatment durations longer than 5 years for patients with postmenopausal osteoporosis. This review gives advice to aid clinicians in the management of patients with incipient or complete atypical fractures.
Summary: Extremely limited evidence is available for how best to manage patients with atypical fractures. A comprehensive metabolic approach for the management of patients on long-term bisphosphonates will help to prevent oversuppression of bone remodeling that is implicated in the pathogenesis of these fractures.
- PMID: 22643705
Donnelly awarded ASBMR Junior Faculty Osteoporosis Research Award
The American Society for Bone and Mineral Research has awarded Prof. Donnelly the 2012 Junior Faculty Osteoporosis Research (JFOR) Award to support her proposal, “Spectroscopic and Biochemical Markers of Bone Quality in Patients with Atypical Femoral Fractures.” She will accept the award at the ASBMR annual meeting on 14 October 2012.
Donnelly E, Meredith DS, Nguyen JT, Gladnick BP, Rebolledo BJ, Shaffer AD, Lorich DM, Lane JM, and Boskey AL. Reduced bone tissue compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures. J Bone Miner Res.
DOI
Abstract
Reduction of bone turnover with bisphosphonate treatment alters bone mineral and matrix properties. Our objective was to investigate the effect of bisphosphonate treatment on bone tissue properties near fragility fracture sites in the proximal femur in postmenopausal women with osteoporosis. The mineral and collagen properties of cortico-cancellous biopsies from the proximal femur were compared in bisphosphonate-naive (-BIS, n = 20) and bisphosphonate-treated (+BIS, n = 20, duration 7 ± 5 y) patients with intertrochanteric (IT) and subtrochanteric (ST) fractures using Fourier transform infrared imaging (FTIRI). The mean values of the FTIRI parameter distributions were similar across groups, but the widths of the parameter distributions tended to be reduced in the +BIS group relative to the -BIS group. Specifically, the distribution widths of the cortical collagen maturity and crystallinity were reduced in the +BIS group relative to those of the -BIS group by 28% (+BIS 0.45 ± 0.18 vs. -BIS 0.63 ± 0.28, p = 0.03) and 17% (+BIS 0.087 ± 0.012 vs. -BIS 0.104 ± 0.036, p = 0.05), respectively. When the tissue properties were examined as a function of fracture morphology within the +BIS group, the FTIR parameters were generally similar regardless of fracture morphology. However, the cortical mineral:matrix ratio was 8% greater in tissue from patients with atypical ST fractures (n =6) than that of patients with typical (IT or spiral ST) fractures (n = 14) (Atypical 5.6 ± 0.3 vs. Typical 5.2 ± 0.5, p = 0.03). Thus, although the mean values of the FTIR properties were similar in both groups, the tissue in bisphosphonate-treated patients had a more uniform composition than that of bisphosphonate-naïve patients. The observed reductions in mineral and matrix heterogeneity may diminish tissue-level toughening mechanisms. © 2011 American Society for Bone and Mineral Research
Keywords
Fourier transform infrared imaging; cortical bone; material properties; hip fracture; atypical subtrochanteric fracture
Donnelly E, Meredith DS, Nguyen JT, and Boskey AL. Bone tissue composition varies across anatomic sites in the proximal femur and the iliac crest. J Orthop Res.
DOI
Abstract
The extent to which bone tissue composition varies across anatomic sites in normal or pathologic tissue is largely unknown, although pathologic changes in bone tissue composition are typically assumed to occur throughout the skeleton. Our objective was to compare the composition of normal cortical and trabecular bone tissue across multiple anatomic sites. The composition of cadaveric bone tissue from three anatomic sites was analyzed using Fourier transform infrared imaging: iliac crest (IC), greater trochanter (GT), and subtrochanteric femur (ST). The mean mineral:matrix ratio was 20% greater in the subtrochanteric cortex than in the cortices of the iliac crest (p = 0.004) and the greater trochanter (p = 0.02). There were also trends toward 30% narrower crystallinity distributions in the subtrochanteric cortex than in the greater trochanter (p = 0.10) and 30% wider crystallinity distributions in the subtrochanteric trabeculae than in the greater trochanter (p = 0.054) and the iliac crest (p = 0.11). Thus, the average cortical tissue mineral content and the widths of the distributions of cortical crystal size/perfection differ at the subtrochanteric femur relative to the greater trochanter and the iliac crest. In particular, the cortex of the iliac crest has lower mineral content relative to that of the subtrochanteric femur and may have limited utility as a surrogate for subtrochanteric bone. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Keywords
iliac crest; subtrochanteric femur; Fourier transform infrared imaging; cortical bone; material properties
Donnelly E. (2011) Methods for assessing bone quality. Clin Orthop Relat Res 469: 2128-2138.
DOI
Abstract
Bone mass, geometry, and tissue material properties contribute to bone structural integrity. Thus, bone strength arises from both bone quantity and quality. Bone quality encompasses the geometric and material factors that contribute to fracture resistance.This review presents an overview of the methods for assessing bone quality across multiple length scales, their outcomes, and their relative advantages and disadvantages.A PubMed search was conducted to identify methods related to bone mechanical testing, imaging, and compositional analysis. Using various exclusion criteria, articles were selected for inclusion.Methods for assessing mechanical properties include whole-bone, bulk tissue, microbeam, and micro- and nanoindentation testing techniques. Outcomes include structural strength and material modulus. Advantages include direct assessment of bone strength; disadvantages include specimen destruction during testing. Methods for characterizing bone geometry and microarchitecture include quantitative CT, high-resolution peripheral quantitative CT, high-resolution MRI, and micro-CT. Outcomes include three-dimensional whole-bone geometry, trabecular morphology, and tissue mineral density. The primary advantage is the ability to image noninvasively; disadvantages include the lack of a direct measure of bone strength. Methods for measuring tissue composition include scanning electron microscopy, vibrational spectroscopy, nuclear magnetic resonance imaging, and chemical and physical analytical techniques. Outcomes include mineral density and crystallinity, elemental composition, and collagen crosslink composition. Advantages include the detailed material characterization; disadvantages include the need for a biopsy.Although no single method can completely characterize bone quality, current noninvasive imaging techniques can be combined with ex vivo mechanical and compositional techniques to provide a comprehensive understanding of bone quality.
Boskey AL, Donnelly E, Kinnett JG. (2011) Bone quality: From bench to bedside: Opening editorial comment. Clin Orthop Relat Res 469: 2087-2089.
DOI
Abstract
The term ‘‘bone quality’’ is frequently used by clinicians,
basic scientists, and engineers. However, do they mean the
same thing? In this symposium, we asked the authors what
they meant by ‘‘bone quality,’’ and as the reader will discover,
there are many aspects of bone quality that vary in
importance and scope with the person providing the definition.
In recent years, numerous reviews have explored
and described bone quality (eg, [2–25, 29]) and some have
discussed therapies for fragility fractures [13], but none has
emphasized the transition from the bench to the bedside
(and the operating room). In fact, the majority of these
reviews of bone quality are either engineering or basic
bone biology articles [3–6, 10, 11, 16], including imaging
techniques [3, 8, 12, 17, 20, 25], or papers on how to treat
osteoporosis [5, 7, 9, 15, 18, 19, 21, 23, 24]. Here too we
review those topics, providing recent research data from
leaders in the field. This symposium reviews and makes
suggestions for appropriate management of individuals
with impaired bone quality because the orthopaedic surgeon
sees cases where the quality of the bone is abnormal,
whether in patients with osteoporosis, osteopetrosis, cancer
[14], or a metabolic problem, such as diabetes [22], kidney
disease [29], or rheumatoid arthritis, and because little
guidance is available on pre- and postsurgical management
of these cases.
Donnelly Research Lab 
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