Table 3.
Study reporting quality evaluation results and information recorded for the 62 studies that met the systematic review inclusion criteria for canine osteoarthritis and predisposing conditions risk factors.
| References | Risk factor paper findings | Direction of risk | Reporting quality evaluation (QE) category and score | Type of study | Overall sample size | Control sample size | Sample size calculated |
|---|---|---|---|---|---|---|---|
| Cruciate ligament literature evaluation | |||||||
| Adams et al. (20) | Females | Increased (OR 2 compared to males) | H-9 | R-CC | 1,368 | 1,179 | N |
| Rottweiler breed | Increased (OR 5 compared to crossbreeds) | ||||||
| Obesity | Increased (OR 3.8 compared to healthy weight) | ||||||
| Younger dogs | Decreased (OR 0.2 compared to dogs >8) | ||||||
| Baird et al. (21) | Regions on Chr 3 and 33 (most significant) | Decreased (OR 0.1–0.2) | M-7 | R-CC | 749 | 456 | N |
| Regions on Chr 1 (most significant) | Increased (OR 5.96) | ||||||
| Baird et al. (22) | Collagen genes significantly associated | Increased | M-7 | R-CC | 271 | 172 | N |
| Baker et al. (23) | Multiple genetic loci (~172) contribution | Increased | M-7 | R-CS | 237 | 139 | Y |
| Heritability 0.48 | |||||||
| Baker et al. (24) | Significant loci on ROR2 (Cartilage and bone development) | Increased | M-7 | R-CS | 222 | 69 | N |
| Significant loci on DOCK2 gene (immune cell migration) | Increased | ||||||
| Clements et al. (25) | Neutered | Increased | H-8 | R-CC | 17 | 12 | N |
| COL5A1 and RPL13A upregulated in | Increased | ||||||
| 14 genes upregulated in rupture | Increased | ||||||
| 2 genes down regulated in rupture | Increased | ||||||
| Duval et al. (26) | Large breeds (9 predisposed) | Increased (OR range 2.15–15.33) | H-10 | R-CC | 1,005 | 804 | N |
| Neutered | Increased | ||||||
| Greater body weight | Increased | ||||||
| Grierson et al. (27) | Rottweilers Golden Retriever | Increased (OR 1.89) Decreased (OR 0.36) | H-9 | R-CS | 511 | N/A | N |
| Males | Increased (OR 1.72) | ||||||
| Overweight | Increased (OR 1.77) | ||||||
| Guenego et al. (28) | High tibial anatomical-mechanical axis angle | Increased | H-9 | R-CS/CC | 274 | 72 | N |
| Inauen et al. (29) | Lower tibial tuberosity width | Decreased | H-8 | R-CS | 219 | 73 | N |
| Greater body weight | Increased | ||||||
| Larger proximal tibial tuberosity angle | Increased | ||||||
| Younger | Decreased | ||||||
| Morris and Lippowitz (30) | Larger tibial plateau angle | Increased | H-8 | P-C | 87 | 31 | N |
| Necas et al. (31) | Breeds: Am. Staff terrier, Rottweiler, | Increased | H-9 | R-CS | 183 | N/A | N |
| Chow Chow, St Bernard, Bullmastiff | Increased | ||||||
| German shorthaired pointer, Boxer | Increased | ||||||
| German Shepherds | Decreased | ||||||
| Pecin et al. (32) | 5–8 years | Increased | M-7 | R-CS | 117 | N/A | N |
| Mixed breeds and Labradors | Increased | ||||||
| Taylor-Brown et al. (16) | Neutered females | Increased | H-9 | R-CC | 2,828 | 1,875 | Y |
| >3 years | Increased (OR 2.1) | ||||||
| Rottweiler, West Highland Terrier, Golden Retrievers, Yorkshire Terriers, and Staffordshire Bull Terriers | Increased (OR 5.4, 2.5, 1.9, 1.8, respectively) | ||||||
| Cocker Spaniels | Decreased (0.4) | ||||||
| Increasing body weight | Increased (OR 3.4) | ||||||
| Insured | Increased (OR 4.0) | ||||||
| Townsend et al. (33) | Steep medial tibial plateau midsagittal radius of curvature (m-TPr) angle | Increased | M-7 | R-CS | 18 | 18 | N |
| Whitehair et al. (34) | 7–10 years | Increased | H-10 | R-CC | 602,317 | 591,548 | N |
| Neutered | Increased | ||||||
| Females | Increased | ||||||
| Rottweiler, Newfoundland, Staff terrier | Increased | ||||||
| Old English Sheepdogs, Basset Hounds, and Dachshunds | Decreased | ||||||
| Greater body weight | Increased (>22 kg) | ||||||
| Wilke et al. (35) | 86 markers associated with CCLR traits | Increased | M-6 | R-CS | 90 | N/A | N |
| 4 associated markers on chr 3, 5, 13, and 24 | Increased | ||||||
| Dysplasia literature evaluation | |||||||
| Beuing et al. (36) | Males | Increased | H-8 | R-CS | 2,114 | N/A | N |
| Heritability estimate 0.28 | Increased | ||||||
| Cardinet et al. (37) | Low Pelvic muscle mass index | Increased | H−8 | P-C | 82 | N/A | N |
| Choi et al. (38) | High distraction index | Increased | M-5 | R-CS | 87 | N/A | N |
| Greater weight | Increased | ||||||
| Dogs kept indoors through growth | Increased | ||||||
| Clements et al. (39) | 5 SNPs associated with risk | Increased | M-5 | R-CC | 647 | 438 | N |
| 5 SNPs associated with protection | Decreased | ||||||
| 8 haplotypes as risk (5) or protectors (3) | Increased and Decreased | ||||||
| Coopman et al. (40) | German Shepherd dog, Golden and Labrador retriever and Bernese Mountain dog (Hip) | Increased (prevalence) | M-6 | R-CS | 7,506 | N/A | N |
| Rottweilers, Newfoundland, and Sharpei (elbow) | Increased (prevalence) | ||||||
| Hou et al. (41) | Boykin Spaniel and St Bernard (Hip) | Increased (Incidence) | H−8 | R-CS | 895,864 | N/A | N |
| Siberian Husky and Afghan Hound (Hip) | Decreased (Incidence) | ||||||
| Rottweiler (elbow) | Increased (Incidence) | ||||||
| Rhodesian Ridgeback (Elbow) | Decreased (Incidence) | ||||||
| Males (elbow) | Increased | ||||||
| 3–5 years old | Increased | ||||||
| Kealy et al. (42) | Non-limited feeding | Increased | M-7 | P-C | 48 | N/A | N |
| Krontveit et al. (43) | Born Spring and Summer | Decreased | H-8 | P-C | 501 | N/A | N |
| Urban/suburban home (breeder home) | Increased | ||||||
| Exercise on soft ground, daily stair use | Increased | ||||||
| Off leash exercise (from 0 to 3 months) | Decreased | ||||||
| Lavrijsen et al. (44) | Bullmastiff, Boxer, and Italian Corso dog most prevalent | Increased (prevalence) | H-9 | R-CS | 35,046 | N/A | N |
| Golden Retrievers—Female | Increased (prevalence) | ||||||
| Labrador Retriever—Males | Increased (prevalence) | ||||||
| Lavrijsen et al. (45) | Associated regions on chr 8 | Increased | H-9 | R-CC | 122 | NS | N |
| Candidate genes LAMA2, LRR1, and COL6A3 (disruption in etiology of hip) | Increased | ||||||
| Leppanen et al. (46) | Born spring and summer | Decreased | H-8 | P-CS | 10,335 | N/A | N |
| Older dogs | Increased | ||||||
| Loder and Todhunter (47) | Females | Increased (OR 1.05) | H-8 | R-CS | 921,046 | N/A | N |
| Born in spring and winter | Increased (OR 1.14 and 1.13) | ||||||
| Working dogs | Increased (OR 1.88) | ||||||
| Oberbauer et al. (48) | Increasing age | Increased | H-9 | R-CS | 1,331,981 | N/A | N |
| Heritability 0.57 | Increased | ||||||
| Priester and Mulvihill (49) | Large and giant breeds | Increased (Relative risk 3.6 and 10.2) | H-9 | R-CS | 1,193 | N/A | N |
| Small and medium breeds | Decreased (Relative risk 0.2) | ||||||
| Sallander et al. (50) | Exercise by running after balls/sticks | Increased (OR 2.4) | M-6 | R-CC | 292 | NS | N |
| High fat intake/energy from fat | Increased | ||||||
| Overfeeding/ High body weight | Increased | ||||||
| Todhunter et al. (51) | HHIP, DACT2, and WIF1 expression | Decreased | M-6 | R-CC | 32 | 8 | N |
| SPON 1, FBN2, EMILIN3, ACAN, IGF1, CILP2, COL11A1, COL8A1, HAPLN, PLA2F, TNFRSF, TMEM, IGFBP expression | Increased | ||||||
| Torres de la riva et al. (26) | Early neutered males | Increased | M-7 | R-C | 1,518 | N/A | N |
| Witsberger et al. (52) | Neutered males | Increased (OR 1.21) | H-8 | R-CS | 1,243,681 | N/A | N |
| 2 months−1 year and 1–4 years | Increased (OR 1.22 and 1.48) | ||||||
| Large and Giant breeds | Increased | ||||||
| Wood and Lakhani (53) | Born July to October | Decreased | M-7 | R-CS | 9,657 | N/A | N |
| Parents with high hip scores (parental genetic effect) | Increased | ||||||
| Worth et al. (54) | Born Autumn (March and April, New Zealand) | Decreased | H-9 | R-CS | 5,722 | N/A | N |
| Osteoarthritis literature evaluation | |||||||
| Anderson et al. (9) | Rottweiler, Dogue de Bordeaux, and Old English Sheepdogs | Increased (OR 3.1, 2.8, and 2.8) | H-8 | R-CS and CC | 455,557 | 451,361 | Y |
| Insured dogs, Neutered dogs | Increased (OR 2.02, 1.8) | ||||||
| Increasing age (>3 years) and high body weight | Increased (OR 3.55–53.89 and 2.29) | ||||||
| Andrysikova et al. (55) | High levels of GAGs | Increase | H-8 | R-CC | 36 | 5 | N |
| Higher GAGs in obese dogs | Increase | ||||||
| Grondalen and Lingaas (56) | Males | Increased | M-6 | P-CS | 2,046 | N/A | N |
| Dogs with at least one parent with osteoarthritis | Increased (Relative risk 1–6) | ||||||
| Hays et al. (57) | Males (increased hip score and risk of osteoarthritis) | Increased | M-7 | P-CS | 137 | N/A | N |
| Additive inheritance | |||||||
| Hegemann et al. (58) | Synovial 5D4 and TIMP-1 increased (ACLR) | Increased | H-8 | R-CC | 133 | 30 | N |
| Higher serum 5D4 and 10-fold lower serum TIMP-1 levels (FPC) | Increased | ||||||
| Synovial 5D4 and TIMP-1 were upregulated in dogs (patella luxation) | Increased | ||||||
| Kealy et al. (59) | Non-restricted feeding | Increased | H-8 | P-C | 48 | N/A | N |
| Greater norberg angle and early joint laxity | Increased | ||||||
| Kealy et al. (60) | Higher body weight | Increased | H-8 | P-C | 48 | N/A | N |
| Non-restricted feeding | Increased | ||||||
| Maccoux et al. (61) | IL-1b expression in synovial fluid and fat pad | Increased | M-7 | R-CC | 13 | 5 | N |
| IL-6 expression in synovial membrane | Increased | ||||||
| Synovial membrane IL-8 expression | Decreased | ||||||
| IL-10 gene expression in synovial membrane | Increased | ||||||
| Mayhew et al. (62) | Caudolateral curvilinear osteophytes present | Increased (7.9 times) | M-7 | R-CS | 25,968 | N/A | N |
| High distraction index | Increased | ||||||
| Powers et al. (63) | Caudolateral curvilinear osteophytes present | Increased (3.7 times) | M-7 | P-C | 48 | N/A | N |
| Non-restricted feeding | Increased | ||||||
| Ramirez-Flores et al. (64) | Females | Increased | M-6 | P-C | 44 | N/A | N |
| Body weight >10 kg | Increased | ||||||
| Runge et al. (65) | Non-restricted feeding | Increased | M-7 | P-C | 48 | N/A | N |
| Runge et al. (66) | High distraction index | Increased (OR by breed) | H-8 | R-CS | 4,349 | N/A | N |
| Higher weight | Increased | ||||||
| Older dogs | Increased | ||||||
| Smith et al. (15) | High distraction index | Increased | H-9 | R-CS | 15,742 | N/A | N |
| Weight | Increased | ||||||
| German shepherd dogs | Increased (4.95 times) | ||||||
| Increasing age | Increased | ||||||
| Smith et al. (67) | Non-restricted feeding | Increased | H-8 | P-C | 48 | N/A | N |
| Szabo et al. (68) | Circumferential femoral head osteophytes present | Increased | M-7 | P-C | 48 | N/A | N |
| Osteochondritis dissecans literature evaluation | |||||||
| Guthrie and Pidduck (69) | Males | Increased | M-6 | R-CS | 46 | N/A | N |
| Multifactorial mode of inheritance | |||||||
| Higher heritability in males | Increased | ||||||
| Ohlerth et al. (70) | Osteophyte formation | Increased | H-8 | R-CS | 351 | N/A | H |
| Slater et al. (71) | Drinking well-water | Increased | H-10 | R-CC | 91 | 60 | N |
| Playing with other dogs daily | Increased | ||||||
| Feeding specialty dry food | Decreased | ||||||
| High dietary calcium | Increased | ||||||
| Patella luxation literature evaluation | |||||||
| Bound et al. (72) | Small Breeds most prevalent | Increased | H-10 | R-CS and CC | 155 | 42 | Y |
| Maeda et al. (73) | Toy Poodles, Pomeranian, Yorkshire Terriers, and Shibas | Increased | M-7 | R-CS | 2,048 | N/A | N |
| Genetic- higher risk if littermate has PL | Increased (16.2-fold) | ||||||
| Nilsson et al. (74) | Heritibality: 0.25 (Chihuahua) 0.21 (Bichon Frise) | Increased | M-6 | R-CS | 3,095 | N/A | N |
| O'Neill et al. (75) | Small Breeds- Pomeranian, Chihuahua, Yorkshire Terrier, and French Bulldog | Increased (OR 6.5; 5.9; 5.5 and 5.4) | H-9 | R-CS | 206,482 | N/A | Y |
| >12 years | Decreased (OR 0.4) | ||||||
| Females | Increased (OR 1.3) | ||||||
| Neutered | Increased (OR 2.4) | ||||||
| Insured | Increased (OR 1.9) | ||||||
| Srinarang et al. (76) | Significant SNPs in DAG1 gene | Increased | M-7 | R-CC | 91 | 30 | N |
| Wangdee et al. (77) | Heritability 0.44 | Increased | M-7 | R-CS | 339 | N/A | N |
| SNP Chr 13 | Increased | +R-CC | 96 | 48 | |||
C, cohort; CC, case-control; CS, cross sectional; H, high; M, medium; N, no; N/A, not applicable; NS, not stated; OR, odds ratio; P, prospective; R, retrospective; Y, yes.