@article{morales2020learning,
  title={Learning osteoarthritis imaging biomarkers from bone surface spherical encoding},
  author={Morales Martinez, Alejandro and Caliva, Francesco and Flament, Io and others},
  journal={Magnetic resonance in medicine},
  volume={84},
  number={4},
  pages={2190--2203},
  year={2020},
  publisher={Wiley Online Library}
}

@inproceedings{milletari2016v,
  title={V-net: Fully convolutional neural networks for volumetric medical image segmentation},
  author={Milletari, Fausto and Navab, Nassir and Ahmadi, Seyed-Ahmad},
  booktitle={2016 fourth international conference on 3D vision (3DV)},
  pages={565--571},
  year={2016},
  organization={IEEE}
}

@inproceedings{caliva2020breaking,
  title={Breaking Speed Limits with Simultaneous Ultra-Fast MRI Reconstruction and Tissue Segmentation},
  author={Caliv{\'a}, Francesco and Leynes, Andrew P and Shah, Rutwik and others},
  booktitle={Medical Imaging with Deep Learning},
  pages={94--110},
  year={2020},
  organization={PMLR}
}

@article{kingma2014adam,
  title={Adam: A method for stochastic optimization},
  author={Kingma, Diederik P and Ba, Jimmy},
  journal={arXiv preprint arXiv:1412.6980},
  year={2014}
}

@article{hunter_longitudinal_2016,
	title = {Longitudinal validation of periarticular bone area and {3D} shape as biomarkers for knee {OA} progression? {Data} from the {FNIH} {OA} {Biomarkers} {Consortium}},
	volume = {75},
	issn = {1468-2060},
	shorttitle = {Longitudinal validation of periarticular bone area and {3D} shape as biomarkers for knee {OA} progression?},
	doi = {10.1136/annrheumdis-2015-207602},
	abstract = {OBJECTIVE: To perform a longitudinal validation study of imaging bone biomarkers of knee osteoarthritis (OA) progression.
METHODS: We undertook a nested case-control study within the Osteoarthritis Initiative in knees (one knee per subject) with a Kellgren and Lawrence grade of 1-3. Cases were defined as knees having the combination of medial tibiofemoral radiographic progression and pain progression at the 24-month, 36-month or 48-month follow-up compared with baseline. Controls (n=406) were eligible knees that did not meet both endpoint criteria and included 200 with neither radiographic nor pain progression, 103 with radiographic progression only and 103 with pain progression only. Bone surfaces in medial and lateral femur, tibia and patella compartments were segmented from MR images using active appearance models. Independent variables of primary interest included change from baseline to 24 months in (1) total area of bone and (2) position on three-dimensional (3D) bone shape vectors that discriminate OA versus non-OA shapes. We assessed the association of bone markers changes over 24 months with progression using logistic regression.
RESULTS: 24-month changes in bone area and shape in all compartments were greater in cases than controls, with ORs of being a case per 1 SD increase in bone area ranging from 1.28 to 1.71 across compartments, and per 1 SD greater change in 3D shape vectors ranging from 1.22 to 1.64. Bone markers were associated most strongly with radiographic progression and only weakly with pain progression.
CONCLUSIONS: In knees with mild-to-moderate radiographic OA, changes in bone area and shape over 24 months are associated with the combination of radiographic and pain progression over 48 months. This finding of association with longer term clinical outcome underscores their potential for being an efficacy of intervention biomarker in clinical trials.},
	language = {eng},
	number = {9},
	journal = {Annals of the Rheumatic Diseases},
	author = {Hunter, David and Nevitt, Michael and Lynch, John and Kraus, Virginia Byers and Katz, Jeffrey N. and Collins, Jamie E. and Bowes, Mike and Guermazi, Ali and Roemer, Frank W. and Losina, Elena and {FNIH OA Biomarkers Consortium}},
	month = sep,
	year = {2016},
	pmid = {26483253},
	keywords = {Aged, Arthralgia, Biomarkers, Case-Control Studies, Disease Progression, Female, Femur, Follow-Up Studies, Humans, Knee Osteoarthritis, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Osteoarthritis, Osteoarthritis, Knee, Patella, Tibia, Time Factors},
	pages = {1607--1614},
	file = {Submitted Version:C\:\\Users\\alemo\\Zotero\\storage\\2SBWW58U\\Hunter et al. - 2016 - Longitudinal validation of periarticular bone area.pdf:application/pdf}
}

@article{cross_global_2014,
	title = {The global burden of hip and knee osteoarthritis: estimates from the {Global} {Burden} of {Disease} 2010 study},
	volume = {73},
	shorttitle = {The global burden of hip and knee osteoarthritis},
	abstract = {Objective To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions.
Methods Systematic reviews were conducted to source age-speciﬁc and sex-speciﬁc epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were deﬁned to derive disability weights (DWs) and severity distribution ( proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs).
Results Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global agestandardised prevalence of knee OA was 3.8\% (95\% uncertainty interval (UI) 3.6\% to 4.1\%) and hip OA was 0.85\% (95\% UI 0.74\% to 1.02\%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42\% of total DALYs) to 17.1 million in 2010 (0.69\% of total DALYs).
Conclusions Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world’s population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.},
	language = {en},
	number = {7},
	urldate = {2019-09-17},
	journal = {Annals of the Rheumatic Diseases},
	author = {Cross, Marita and Smith, Emma and Hoy, Damian and others},
	year = {2014},
	pages = {1323--1330},
	file = {Cross et al. - 2014 - The global burden of hip and knee osteoarthritis .pdf:C\:\\Users\\alemo\\Zotero\\storage\\6BATWD3Q\\Cross et al. - 2014 - The global burden of hip and knee osteoarthritis .pdf:application/pdf}
}

@article{hootman_projections_2006,
	title = {Projections of {US} prevalence of arthritis and associated activity limitations},
	volume = {54},
	copyright = {Copyright © 2006 by the American College of Rheumatology},
	issn = {1529-0131},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/art.21562},
	doi = {10.1002/art.21562},
	abstract = {Objective To update the projected prevalence of self-reported, doctor-diagnosed arthritis and arthritis-attributable activity limitations among US adults ages 18 years and older from 2005 through 2030. Methods Baseline age- and sex-specific prevalence rates of arthritis and activity limitation, using the latest surveillance case definitions, were estimated from the 2003 National Health Interview Survey, which is an annual, cross-sectional, population-based health interview survey of ∼31,000 adults. These estimates were used to calculate projected arthritis prevalence and activity limitations for 2005–2030 using future population projections obtained from the US Census Bureau. Results The prevalence of self-reported, doctor-diagnosed arthritis is projected to increase from 47.8 million in 2005 to nearly 67 million by 2030 (25\% of the adult population). By 2030, 25 million (9.3\% of the adult population) are projected to report arthritis-attributable activity limitations. In 2030, {\textgreater}50\% of arthritis cases will be among adults older than age 65 years. However, working-age adults (45–64 years) will account for almost one-third of cases. Conclusion By 2030, the number of US adults with arthritis and its associated activity limitation is expected to increase substantially, resulting in a large impact on individuals, the health care system, and society in general. The growing epidemic of obesity may also significantly contribute to the future burden of arthritis. Improving access and availability of current clinical and public health interventions aimed at improving quality of life among persons with arthritis through lifestyle changes and disease self-management may help lessen the long-term impact.},
	language = {en},
	number = {1},
	urldate = {2019-06-25},
	journal = {Arthritis \& Rheumatism},
	author = {Hootman, Jennifer M. and Helmick, Charles G.},
	year = {2006},
	pages = {226--229},
	file = {Full Text PDF:C\:\\Users\\alemo\\Zotero\\storage\\JKMXL8RR\\Hootman and Helmick - 2006 - Projections of US prevalence of arthritis and asso.pdf:application/pdf;Snapshot:C\:\\Users\\alemo\\Zotero\\storage\\WNF77CGE\\art.html:text/html}
}

@article{cisternas_alternative_2016,
	title = {Alternative {Methods} for {Defining} {Osteoarthritis} and the {Impact} on {Estimating} {Prevalence} in a {US} {Population}-{Based} {Survey}},
	volume = {68},
	issn = {2151-464X},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769961/},
	doi = {10.1002/acr.22721},
	abstract = {Objective
Provide a contemporary estimate of osteoarthritis (OA) by comparing accuracy and prevalence of alternative definitions of OA.

Methods
The Medical Expenditure Panel Survey (MEPS) household component (HC) records respondent-reported medical conditions as open-ended responses; professional coders translate these responses into ICD-9-CM codes for the medical conditions files. Using these codes and other data from the MEPS-HC medical conditions files, we constructed three case definitions of OA and assessed them against medical provider diagnoses of ICD-9-CM 715 [osteoarthrosis and allied disorders] in a MEPS subsample. The three definitions were: 1) strict = ICD-9-CM 715; 2) expanded = ICD-9-CM 715, 716 [other and unspecified arthropathies], OR 719 [other and unspecified disorders of joint]); and 3) probable = strict OR expanded + respondent-reported prior diagnosis of OA or other arthritis excluding rheumatoid arthritis (RA).

Results
Sensitivity and specificity of the three definitions were: strict – 34.6\% and 97.5\%; expanded – 73.8\% and 90.5\%; and probable – 62.9\% and 93.5\%.

Conclusion
The strict definition for OA (ICD-9-CM 715) excludes many individuals with OA. The probable definition of OA has the optimal combination of sensitivity and specificity relative to the two other MEPS-based definitions and yields a national annual estimate of 30.8 million adults with OA (13.4\% of US adult population) for 2008 – 2011.},
	number = {5},
	urldate = {2019-06-24},
	journal = {Arthritis care \& research},
	author = {Cisternas, Miriam G. and Murphy, Louise and Sacks, Jeffrey J. and Solomon, Daniel H. and Pasta, David J. and Helmick, Charles G.},
	month = may,
	year = {2016},
	pmid = {26315529},
	pmcid = {PMC4769961},
	pages = {574--580},
	file = {PubMed Central Full Text PDF:C\:\\Users\\alemo\\Zotero\\storage\\TC7747M4\\Cisternas et al. - 2016 - Alternative Methods for Defining Osteoarthritis an.pdf:application/pdf}
}

@article{muller-gerbl_assessment_1994,
	title = {Assessment of subchondral bone density distribution patterns in patients subjected to correction osteotomy},
	volume = {19},
	journal = {Trans Orth Soc},
	author = {Müller-Gerbl, M and Griebl, S and Putz, R and Goldmann, A and Kuhr, M and Taeger, K},
	year = {1994},
	pages = {574}
}

@book{pauwels_biomechanics_1980,
	address = {Berlin Heidelberg},
	title = {Biomechanics of the {Locomotor} {Apparatus}: {Contributions} on the {Functional} {Anatomy} of the {Locomotor} {Apparatus}},
	isbn = {978-3-642-67140-1},
	shorttitle = {Biomechanics of the {Locomotor} {Apparatus}},
	url = {https://www.springer.com/us/book/9783642671401},
	abstract = {The contents of this book are based almost exclusively on purely anatomical researches. These were stimulated by questions posed in clinical practice. The results are directed to practicing surgeons. Their chronological sequence leads to a step by step development of theoretical bases and to a progressive rejection of old conceptions. Especially in the field of orthopaedic surgery, a responsible attitude is possible neither without solid anatomical knowledge, nor without an idea of functional relationships. W. Roux had already demonstrated this and he wanted his works of functional anatomy to be considered from this point of view. He above all preoccupied himself with a uniform theory of functional adaptation. Thus it is understandable that the theories ofRoux formed the basis from which to start. Our own researches seemed at first to corroborate the ideas of Roux, at least in part. This is still evident in the monograph concerning fractures of the femoral neck. Later it appeared that ST. KROMPECHER had made a step forwards in the matter of chondrogenesis when he abandoned the shear theory postulated by Roux and held that compression was the only effective stimulus for the forma­ tion of cartilage. The research concerning the healing of fractures relies partly on the theory of KROMPECHER which was new at that time. But ultimately more and more discoveries could no longer be explained by this conception which was only slightly different from the older theories (1. WOLF, W. Roux, W.},
	language = {en},
	urldate = {2019-06-13},
	publisher = {Springer-Verlag},
	author = {Pauwels, Friedrich},
	year = {1980},
	file = {Snapshot:C\:\\Users\\alemo\\Zotero\\storage\\6F4FDX36\\9783642671401.html:text/html}
}

@article{lynch_association_2009,
	title = {The association of proximal femoral shape and incident radiographic hip {OA} in elderly women},
	volume = {17},
	issn = {1063-4584},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678721/},
	doi = {10.1016/j.joca.2009.04.011},
	abstract = {Purpose
Variations in femoral head shape are reported to predict incident hip osteoarthritis (OA). This study evaluated if proximal femur shape at baseline was a risk factor for incident radiographic hip OA (RHOA) after 8.3 years of follow-up in a cohort of elderly Caucasian women.

Methods
Supine pelvic radiographs were obtained as part of the Study of Osteoporotic Fractures (SOF) at baseline and Visit 5 (8.3 years later), and were scored for RHOA. A nested case–control study was performed: hips were eligible for inclusion if they had no prevalent RHOA in either hip at baseline. Cases of incident RHOA were defined as no RHOA at baseline and RHOA in their right hip present at Visit 5 [or right total hip replacement (THR) for OA between baseline for follow-up] and a random selection of one half of all incident RHOA cases plus right THR cases (n = 102) were chosen. A random selection (n = 249) of control subjects who had no RHOA in their right hip at both baseline and follow-up visit were included for comparison., The shape of the right proximal femur was outlined on a digitized baseline radiograph and a statistical image analysis technique, Active Shape Modeling (ASM), was used to generate 10 unique and independent “modes” or variations in shape, which explained 95\% of the variance in the shape of the proximal femurs studied. Any hip shape was therefore described as the average shape plus a linear combination of these 10 independent modes of variation. The values for each of these 10 modes for each hip analyzed were entered into a logistic regression model as independent predictors of incident RHOA adjusting for covariates.

Results
The incident RHOA cases were slightly taller, heavier and had higher total hip bone mineral density (BMD) than control subjects (P {\textless} 0.05), but were otherwise similar demographically. Results of ASM showed that Modes 1, 2 and 3 together explained 81\% of the variance in proximal femur shape among all subjects analyzed. Modes 3, 5, 9 which accounted for 8.9\%, 3.3\% and 0.8\% of the variance respectively, were significant predictors of incident RHOA with adjusted odds-ratios ranging from 1.61 to 1.99 (P {\textless} 0.001) for every 1 standard deviation (SD) increase in the mode score.

Conclusion
These results suggest that variations in the relative sizes of the femoral head and neck at baseline are modest determinants of incident RHOA in elderly Caucasian women.},
	number = {10},
	urldate = {2019-06-12},
	journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society},
	author = {Lynch, J. A. and Parimi, N. and Chaganti, R. K. and Nevitt, M. C. and Lane, N. E.},
	month = oct,
	year = {2009},
	pmid = {19427402},
	pmcid = {PMC3678721},
	pages = {1313--1318},
	file = {PubMed Central Full Text PDF:C\:\\Users\\alemo\\Zotero\\storage\\Q3PDJGMQ\\Lynch et al. - 2009 - The association of proximal femoral shape and inci.pdf:application/pdf}
}

@article{hu_subchondral_2021,
	title = {Subchondral bone microenvironment in osteoarthritis and pain},
	volume = {9},
	copyright = {2021 The Author(s)},
	issn = {2095-6231},
	url = {https://www.nature.com/articles/s41413-021-00147-z},
	doi = {10.1038/s41413-021-00147-z},
	abstract = {Osteoarthritis comprises several joint disorders characterized by articular cartilage degeneration and persistent pain, causing disability and economic burden. The incidence of osteoarthritis is rapidly increasing worldwide due to aging and obesity trends. Basic and clinical research on osteoarthritis has been carried out for decades, but many questions remain unanswered. The exact role of subchondral bone during the initiation and progression osteoarthritis remains unclear. Accumulating evidence shows that subchondral bone lesions, including bone marrow edema and angiogenesis, develop earlier than cartilage degeneration. Clinical interventions targeting subchondral bone have shown therapeutic potential, while others targeting cartilage have yielded disappointing results. Abnormal subchondral bone remodeling, angiogenesis and sensory nerve innervation contribute directly or indirectly to cartilage destruction and pain. This review is about bone-cartilage crosstalk, the subchondral microenvironment and the critical role of both in osteoarthritis progression. It also provides an update on the pathogenesis of and interventions for osteoarthritis and future research targeting subchondral bone.},
	language = {en},
	number = {1},
	urldate = {2021-04-08},
	journal = {Bone Research},
	author = {Hu, Yan and Chen, Xiao and Wang, Sicheng and Jing, Yingying and Su, Jiacan},
	month = mar,
	year = {2021},
	note = {Number: 1
Publisher: Nature Publishing Group},
	pages = {1--13},
	file = {Full Text PDF:C\:\\Users\\alemo\\Zotero\\storage\\2MHNZFVG\\Hu et al. - 2021 - Subchondral bone microenvironment in osteoarthriti.pdf:application/pdf;Snapshot:C\:\\Users\\alemo\\Zotero\\storage\\UG78MJPV\\s41413-021-00147-z.html:text/html}
}

@article{neogi_clinical_2012,
	title = {Clinical significance of bone changes in osteoarthritis},
	volume = {4},
	abstract = {Osteoarthritis (OA), the most common form of arthritis, is now understood to involve all joint tissues, with active anabolic and catabolic processes. Knee OA in particular is considered to be a largely mechanically-driven disease. As bone adapts to loads by remodeling to meet its mechanical demands, bone alterations likely play an important role in OA development. Subchondral bone changes in bone turnover, mineralization, and volume result in altered apparent and material density of bone that may adversely affect the joint’s biomechanical environment. Subchondral bone alterations such as bone marrow lesions (BMLs) and subchondral bone attrition (SBA) both tend to occur more frequently in the more loaded knee compartments, and are associated with cartilage loss in the same region. Recently, MRI-based 3D bone shape has been shown to track concurrently with and predict OA onset., The contributions of structural abnormalities to the clinical manifestations of knee OA are becoming better understood as well. While a structure-symptom discordance in knee OA is thought to exist, such observations do not take into account all potential factors that can contribute to between-person differences in the pain experience. Using novel methodology, pain fluctuation has been associated with changes in BMLs, synovitis and effusion. SBA has also been associated with knee pain, but the relationship of osteophytes to pain has been conflicting., Understanding the pathophysiologic sequences and consequences of OA pathology will guide rational therapeutic targeting. Importantly, rational treatment targets require understanding what structures contribute to pain as pain is the reason patients seek medical care.},
	number = {4},
	urldate = {2021-04-12},
	journal = {Therapeutic Advances in Musculoskeletal Disease},
	author = {Neogi, Tuhina},
	year = {2012},
	pmid = {22859925},
	pmcid = {PMC3403249},
	pages = {259--267},
	file = {PubMed Central Full Text PDF:C\:\\Users\\alemo\\Zotero\\storage\\2BK5V9MI\\Neogi - 2012 - Clinical significance of bone changes in osteoarth.pdf:application/pdf}
}

@article{donell_subchondral_2019,
	title = {Subchondral bone remodelling in osteoarthritis},
	volume = {4},
	issn = {2058-5241},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549114/},
	doi = {10.1302/2058-5241.4.180102},
	abstract = {Subchondral bone remodelling is an integral part of osteoarthritis and involves the development of subchondral sclerosis seen on plain imaging, along with osteophyte formation.
            
            
              The development of these changes is due to persistent abnormal mechanical stresses which create a cellular and biomolecular response to microfractures in the subchondral bone and osteochondral junction.
            
            
              An early sign is bone marrow lesions seen on MRI scanning. Healing can occur at this stage by correcting the abnormal loads. Persistence leads to what is thought to be a delayed union or nonunion response by the bone.
            
            
              Microfractures of the osteochondral junction, coupled with articular cartilage fissuring and loss, allows synovial fluid to penetrate the subchondral bone along with cytokines and other molecules reacting with the bone cells to increase the pathological effects.
            
            
              This review gives an overview of the current thoughts on subchondral bone remodelling in osteoarthritis that is aimed at orthopaedic surgeons to help in the understanding of the pathogenesis of osteoarthritis and the role of surgical management.
            
          
        , Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180102},
	number = {6},
	urldate = {2021-04-13},
	journal = {EFORT Open Reviews},
	author = {Donell, Simon},
	month = jun,
	year = {2019},
	pmid = {31210964},
	pmcid = {PMC6549114},
	pages = {221--229},
	file = {PubMed Central Full Text PDF:C\:\\Users\\alemo\\Zotero\\storage\\RIK8IAUT\\Donell - 2019 - Subchondral bone remodelling in osteoarthritis.pdf:application/pdf}
}
