Family Predisposition for Rotator Cuff Tear and Other Tendinopathies – A Case-Control Study^[*]

Abstract

Objective To evaluate the prevalence of family history of rotator cuff tear and the presence of tendinopathy in other joints in patients with rotator cuff tears and to compare them with paired controls. To estimate the odds ratio for rotator cuff tear for these two risk factors.

Methods We performed a case-control study comparing patients submitted to treatment for rotator cuff tear with asymptomatic controls. All cases and controls were evaluated by imaging exams and matched by age (±2 years) and gender. We conducted an interview using a standardized questionnaire, and collected data on various risk factors.

Results We evaluated 144 patients, 72 per group. Patients with rotator cuff tears reported a higher number of consanguineous relatives who underwent treatment for the same disease and tendon injuries in other joints compared to the controls (p = 0.005 and p = 0.045 respectively). Individuals with a family history of treatment for rotator cuff tear or with tendinopathies in other joints were more likely to present a rotator cuff tear, with odds ratios of 3.3 (95% confidence interval [95%CI] = 1.4–7.7) and 2.7 (95%CI = 1.1–6.9) respectively.

Conclusions Patients with rotator cuff tear have a higher prevalence of family members with the same disease and tendinopathies or tendon injuries in other joints. The presence of consanguineous relatives with treatment for rotator cuff and tendinopathies in other joints are risk factors for the presence of rotator cuff tears.

Keywords

rotator cuff - genetics - tendinopathy - family history

Introduction

Rotator cuff tendinopathy is the main cause of shoulder[1] pain, and tears of these tendons are prevalent in 20% of the population.[2] The number of patients undergoing surgical treatment for these lesions grows annually,[3] and the arthroscopic repair of the rotator cuff presents satisfactory clinical results in up to 93% of the patients.[4] [5] [6]

The etiology of rotator cuff tear is considered multifactorial.[7] Decreased tendinous vascularization, intrinsic degenerative alterations of the tendon, micro- and macrotraumas, impact syndrome and genetics are factors associated with the development of rotator cuff tear.[8] [9]

Routinely in the clinical practice, physicians observe patients with tendinopathies or tendinous lesions in multiple sites, and there is a possible genetic component involved in the individual's susceptibility to tendinopathy.[10] However, few studies evaluate the familial predisposition or presence of lesion in others joints in patients with a rotator cuff tear.

Initial studies indicate that the presence of family members with rotator cuff tear [11] [12] or the presence of tendinopathies in other joints[13] [14] are risk factors for the development of a rotator cuff tear. However, most studies are epidemiological or use population and hospital databases,[12] [14] [15] with few case-control studies[11] [13] to evaluate these risk factors. We also emphasize that the research of other risk factors as confounding variables and the pairing of the participants by gender and age are rarely employed in case-control studies on this topic.

The objectives of the present study were to evaluate the prevalence of tendinopathy in other joints and family history of cuff tear in patients with rotator cuff tear, to compare them with paired controls, and to estimate the odds ratio of a rotator cuff tear for these two risk factors.

Materials and Methods

Study design, Participants and Eligibility

A case-control study was carried out. We evaluated patients aged between 40 and 65 years with complete rotator cuff tears. The control group consisted of patients treated at the same institution due to traumatic injuries not involving the scapular girdle, with no complaint of shoulder pain, and physical examination without the presence of rotator cuff tear signs. All patients and controls were submitted to an imaging examination (magnetic resonance or ultrasonography) to confirm the tear or the integrity of the rotator cuff. The patients and the controls were paired by age (±2 years) and gender.

The exclusion criteria were: rheumatic diseases, diabetes, previous shoulder surgeries, and previous or current infectious processes in the studied joint. Moreover, patients with traumatic rotator cuff tears were not included, as well as those with partial tears.

The present study was approved by the Ethics in Research Committee of our institution under the number 11186.

Outcomes

Primary outcome

The odds ratio of individuals with a family history of rotator cuff tear to present the same disease was evaluated, as well as the prevalence of relatives who underwent treatment for rotator cuff tear in the case and control groups.

Secondary outcome

The prevalence of tendinopathy or tendinous lesions in other joints was evaluated in individuals with and without rotator cuff tear. We also evaluated the odds ratio of patients with tendinopathies in other joints to have a rotator cuff tear in relation to the control patients.

Valuation Methods

We conducted an interview using a standardized questionnaire, and collected the following data from patients and controls: age, gender, ethnicity, smoking, diagnosis or treatment for systemic arterial hypertension, hypothyroidism, performance of sports with the upper limbs and professional activity with repetitive shoulder abduction movements (≥ two hours per day). We also asked some questions about the personal and family history of rotator cuff tears and other tendinopathies by means of a standardized questionnaire ([Figure 1]).

Fig. 1 Questionnaire on personal and family history for rotator cuff tear and other tendinopathies.

Statistical Analysis

Sample size

The sample calculation used a significance level of 5%, a power of 80%, and a case/control ratio of 1:1.

Using the prevalence rate of rotator cuff tear for the controls and family members of the patients with the same disease, which were obtained from the study by Harvie et al,[11] a total of 72 individuals in each group was required.

Data Analysis

We submitted the continuous variables to a normality assessment using the Kolmogorov-Smirnov test, and a homogeneity assessment through the Levene test. The continuous variables were presented as means and standard deviations, while the categorical variables were expressed as absolute values and percentages. Among the collected variables, age was considered a continuous variable, and the others were considered categorical variables.

The comparison between the cases and controls regarding the different variables was performed by Chi-squared or Fisher exact tests for the categorical variables. For the continuous variables, the Student t test was used if the distribution of the data was parametric, and the Wilcoxon was used if the distribution of the data was non-parametric.

The difference in the prevalence of consanguineous relatives with history of treatment for rotator cuff tear, as well as the presence of tendinopathy and tendinous lesions in other joints in the individuals with rotator cuff tear and in the controls were evaluated by the Chi-squared test. The probability of association of these two risk factors with rotator cuff tears was also calculated as odds ratios, with a 95% confidence interval (95%CI).

For the data analysis, we used the Statistical Package for the Social Sciences (SPSS, IBM Corp., Armonk, NY, US) software, version 21.0, and a significance level of 5%.

Results

We evaluated 144 patients, 72 with complete rotator cuff tear and 72 controls. The cases and controls had mean ages of 53.6 ± 6 and 53.2 ± 6.1 respectively (p = 0.592). Both groups were composed of 48 (66.6%) women and 24 (33.3%) men. The groups did not differ statistically regarding ethnicity, smoking and the presence of systemic arterial hypertension (p = 0.825; p = 0,673; and p = 0,567 respectively). The general characteristics of the sample can be observed in [Table 1].

Table 1

	Cases	Controls	p-value
Age	53.6 ± 6	53.2 ± 6.1	0.592
Gender
Male	24 (33.3%)	24 (33.3%)	> 0.999
Female	48 (66.6%)	48 (66.6%)
Ethnicity
White	48 (66.6%)	46 (63.9%)	0.825
Black	10 (13.9%)	9 (12.5%)
Brown	14 (19.4%)	17 (23.6%)
Smoking
Yes	15 (20.8%)	13 (18.1%)	0.674
No	57 (79.2%)	59 (81.9%)
Systemic arterial hypertension
Yes	17 (23.6%)	20 (27.8%)	0.567
No	55 (76.4%)	52 (72.2%)
Hypothyroidism
Yes	3 (4.2%)	4 (5.6%)	0.698
No	69 (95.8%)	68 (94.4%)
Repetitive work with shoulders
Yes	33 (45.8%)	25 (34.7%)	0.174
No	39 (54.2%)	47 (65.3%)
Sport with use of the upper limbs
Yes	7 (9.7%)	9 (12.5%)	0.596
No	65 (90.3%)	63 (87.5%)

Patients with rotator cuff tear reported the presence of consanguineous patients who underwent treatment for the same disease in a larger number than the control subjects (p = 0.005). Individuals with family history of treatment for rotator cuff tear presented a higher chance of having the same disease, with an odds ratio of 3.3 (95%CI  = 1.4–7.7) ([Table 2]). Among the individuals with rotator cuff tear, 15 (20.8%) reported having at least 1 first-degree family member with the same disease, 7 (9.7%) had at least one second-degree family member with a diagnosis of rotator cuff tear, and 1 (1.4%) patient had first- and second-degree relatives with the same disease. In total, 5 (6.9%) controls reported having a first-degree family member who performed treatment for rotator cuff tear, and 4 (5.6%) had a second-degree family member with the same condition.

Table 2

	Cases	Controls	p-value	Odds ratio
	(n = 72)	(n = 72)		95% confidence interval
Relatives who underwent rotator cuff tear treatment
Yes	23 (31.9%)	9 (12.5%)	0.005	3.3 (1.4–7.7)
No	49 (68.1%)	63 (87.5%)

Tendinopathies or tendon injuries in other joints were more prevalent among patients with rotator cuff tear (p = 0.045). These patients were more likely to develop a rotator cuff tear, with an odds ratio of 2.7 (95%CI = 1.1–6.9) ([Table 3]). Among the patients with rotator cuff tear, the most common tendinopathies or tendinous lesions were lateral epicondylitis and tendinopathy of the calcaneal tendon, which were present in 8 (11.1%) and 7 (9.7%) of the patients respectively.

Table 3

	Cases	Controls	p-value	Odds ratio
	(n = 72)	(n = 72)		95% confidence interval
Presence of tendinopathy or lesions in other joints
Yes	16 (22.2%)	7 (9.7%)	0.045	2.7 (1.1–6.9)
No	56 (77.8%)	65 (90.3%)

Discussion

Our results show that patients with rotator cuff tear have a higher prevalence of family members with the same disease (31.9%) in relation to the controls (12.5%). They also report in greater numbers the presence of tendinopathies or tendon injuries in other joints (22.2%) compared to individuals with intact rotator cuffs (9.7%). The presence of family members with rotator cuff tear and the presence of tendinopathy or tendon injuries in other joints were risk factors for rotator cuff tear, with odds ratios of 3.3 and 2.7 respectively.

Few studies have assessed the possibility of relatives of rotator cuff tear patients having increased risk of developing the same disease.[11] [12] Harvie et al[11] state that siblings of rotator cuff tear patients have 2.4 times more risk of presenting the same lesion, and almost 5 times more risk of having symptoms in relation to the control group. However, the authors of this study evaluated only first-degree relatives (siblings), and used the spouses as controls. Due to the close proximity between cases and controls, environmental and family factors may have interfered in the analysis.

Tashjian et al[12] conducted a study evaluating a population database with health information from the state of Utah, United States, and observed that the family members of rotator cuff tear patients had a greater chance of having the same disease. Relatives with a degree of kinship up to the third degree had an increased risk of rotator cuff tear, especially those who had people in the family with this disease under the age of 40 years. The relative risk for rotator cuff tear among second-degree relatives was of 3.7, and, for the third-degree relatives it was of 1.8. This result and those found by us and by Harvie et a.[11] suggest a familial and genetic predisposition for rotator cuff tears.

For the association between risk factors and a disease, two measures of effect can be used: the relative risk and the odds ratio. The relative risk can be obtained in cohort studies, clinical trials and cross-sectional studies. And the odds ratio can only be obtained directly in case-control studies. The studies conducted by Harvie et al[11] and Tashjian et al[12] were retrospective cohorts, so they used the relative risk as a measure of effect. In turn, the present study was a case-control one, and we used the odds ratio. In general, when the prevalence of a disease in the population is lower than 10%, the odds ratio has a very similar value to that of the relative risk. In the study by Yamamoto et al,[2] the prevalence of rotator cuff tear in patients younger than 60 years of age was of 9%.

Patients with rotator cuff tear have a greater chance of presenting tendinopathies or tendon injuries in other joints.[13] [14] Tashjian et al[13] found that 38.7% of rotator cuff tear patients also report tendinopathies or tendon injuries in other joints, while only 19.3% of the individuals in the control group report the same thing. We found a lower prevalence of tendinopathies in other joints in both groups, but, as the authors of the aforementioned study, we also observed a statistically significant difference between the two groups. Genetic and familial factors are probably involved in the development of tendinous lesions in multiple sites.[13] [15]

Rotator cuff tear, as well as the development of other tendinous lesions, can be considered multifactorial.[7] A certain number of genes may be involved in the etiology of tendinous lesions, each one making a small contribution. The proteins encoded by the multiple genes and the environment participate concomitantly in the development of these injuries.[16] Polymorphisms in the receptor β gene related to estrogen have already been associated with rotator cuff tear[17] [18] and tendinopathy of the posterior tibial tendon.[18] Genes regulating the expression of metalloproteinases and tenascin C, which are important enzymes in the tendinous homeostasis, present polymorphisms associated with rotator cuff tear,[19] [20] tendinopathy of the Achilles tendon,[21] and the posterior tibial tendon.[22] [23] However, the functions of these genes or their coded proteins in the pathophysiology of the tendinous lesions need to be better studied, and other candidate genes may be associated with tendinous lesions.

Our study has some limitations. We did not evaluate all known risk factors for rotator cuff tear, such as body mass index[24] and the patient's dominant upper limb.[2] These factors were not evaluated in our sample, and may act as confounding factors for the results found. We conducted an interview to collect data on the presence of consanguineous relatives with previous treatment for rotator cuff tear and on the current or previous treatment for tendinopathies and tendinous lesions in other joints. Rotator cuff tear patients should probably have better information about personal orthopedic diseases and their relatives, for the lack if it leads to a bias of memory. And as the information was reported by the patient, the diagnoses may also be inaccurate and may have increased the association between these risk factors and the rotator cuff tear. The sample with 144 individuals evaluated may be considered small. Studies with larger samples or among other populations must be performed to confirm the association of these risk factors with rotator cuff tear.

However, we can emphasize that our study performed a pairing of cases and controls by gender and age with a maximum difference of two years. We also evaluated other risk factors that could be confounding variables in our analysis. This methodological refinement was not employed in the few previous studies on the subject. We also performed imaging exams to evaluate the tear or the integrity of the rotator cuff in all study participants. Imaging examinations of the cases and controls were only employed in the study conducted by Harvie et al.[11] Other studies[25] [26] show that up to 60% of patients with rotator cuff tear may be asymptomatic. We can also state that our findings collaborate for the identification of important risk factors for the development of rotator cuff tears and emphasize the need for further research to identify genetic markers for the development of tendinous lesions to enable the identification of susceptible individuals.

Conclusions

Rotator cuff tear patients have a higher prevalence of family members with the same tendinopathies or tendinous lesions in other joints. The presence of consanguineous relatives with treatment for rotator ruff tear and tendinopathies in other joints are risk factors for the presence of rotator cuff tears.

^* Work developed at the Shoulder and Elbow Group, Instituto de Ortopedia e Traumatologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.

• Referências

• 1 Mitchell C, Adebajo A, Hay E, Carr A. Shoulder pain: diagnosis and management in primary care. BMJ 2005; 331 (7525): 1124-1128
• 2 Yamamoto A, Takagishi K, Osawa T. , et al. Prevalence and risk factors of a rotator cuff tear in the general population. J Shoulder Elbow Surg 2010; 19 (01) 116-120
• 3 Malavolta EA, Assunção JH, Beraldo RA, Pinto GMR, Gracitelli MEC, Ferreira Neto AA. Rotator cuff repair in the Brazilian Unified Health System: Brazilian trends from 2003 to 2015. Rev Bras Ortop 2017; 52 (04) 501-505
• 4 Checchia SL, Doneux S, Miyazaki AN. , et al. Avaliação dos resultados obtidos na reparação artroscópica das lesões do manguito rotador. Rev Bras Ortop 2005; 40 (05) 229-238
• 5 Godinho GG, França FO, Freitas JMA. , et al. Avaliação da integridade anatômica por exame de ultrassom e funcional pelo índice de Constant & Murley do manguito rotador após reparo artroscópico. Rev Bras Ortop 2010; 45 (02) 174-180
• 6 Antonio M, Veado C, Afonso I, Filho A, Duarte RG, Leitão I. Avaliação funcional do reparo artroscópico das lesões completas do manguito rotador associado a acromioplastia. Rev Bras Ortop 2008; 43 (11/12): 505-512
• 7 Longo UG, Berton A, Khan WS, Maffulli N, Denaro V. Histopathology of rotator cuff tears. Sports Med Arthrosc Rev 2011; 19 (03) 227-236
• 8 Maffulli N, Longo UG, Berton A, Loppini M, Denaro V. Biological factors in the pathogenesis of rotator cuff tears. Sports Med Arthrosc Rev 2011; 19 (03) 194-201
• 9 DE Giorgi S, Saracino M, Castagna A. Degenerative disease in rotator cuff tears: what are the biochemical and histological changes?. Joints 2014; 2 (01) 26-28
• 10 Magra M, Maffulli N. Genetic aspects of tendinopathy. J Sci Med Sport 2008; 11 (03) 243-247
• 11 Harvie P, Ostlere SJ, Teh J. , et al. Genetic influences in the aetiology of tears of the rotator cuff. Sibling risk of a full-thickness tear. J Bone Joint Surg Br 2004; 86 (05) 696-700
• 12 Tashjian RZ, Farnham JM, Albright FS, Teerlink CC, Cannon-Albright LA. Evidence for an inherited predisposition contributing to the risk for rotator cuff disease. J Bone Joint Surg Am 2009; 91 (05) 1136-1142
• 13 Tashjian RZ, Saltzman EG, Granger EK, Hung M. Incidence of familial tendon dysfunction in patients with full-thickness rotator cuff tears. Open Access J Sports Med 2014; 5: 137-141
• 14 Titchener AG, White JJ, Hinchliffe SR, Tambe AA, Hubbard RB, Clark DI. Comorbidities in rotator cuff disease: a case-control study. J Shoulder Elbow Surg 2014; 23 (09) 1282-1288
• 15 Tashjian RZ, Farnham JM, Granger EK, Teerlink CC, Cannon-Albright LA. Evidence for an Environmental and Inherited Predisposition Contributing to the Risk for Global Tendinopathies or Compression Neuropathies in Patients With Rotator Cuff Tears. Orthop J Sports Med 2016; 4 (04) 2325967116642173
• 16 September AV, Schwellnus MP, Collins M. Tendon and ligament injuries: the genetic component. Br J Sports Med 2007; 41 (04) 241-246 , discussion 246
• 17 Motta GdaR, Amaral MV, Rezende E. , et al. Evidence of genetic variations associated with rotator cuff disease. J Shoulder Elbow Surg 2014; 23 (02) 227-235
• 18 Teerlink CC, Cannon-Albright LA, Tashjian RZ. Significant association of full-thickness rotator cuff tears and estrogen-related receptor-β (ESRRB). J Shoulder Elbow Surg 2015; 24 (02) e31-e35
• 19 Assunção JH, Godoy-Santos AL, Dos Santos MCLG, Malavolta EA, Gracitelli MEC, Ferreira Neto AA. Matrix Metalloproteases 1 and 3 Promoter Gene Polymorphism Is Associated With Rotator Cuff Tear. Clin Orthop Relat Res 2017; 475 (07) 1904-1910
• 20 Kluger R, Burgstaller J, Vogl C, Brem G, Skultety M, Mueller S. Candidate gene approach identifies six SNPs in tenascin-C (TNC) associated with degenerative rotator cuff tears. J Orthop Res 2017; 35 (04) 894-901
• 21 Mokone GG, Gajjar M, September AV. , et al. The guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene is associated with achilles tendon injuries. Am J Sports Med 2005; 33 (07) 1016-1021
• 22 Godoy-Santos A, Cunha MV, Ortiz RT, Fernandes TD, Mattar Jr R, dos Santos MCLG. MMP-1 promoter polymorphism is associated with primary tendinopathy of the posterior tibial tendon. J Orthop Res 2013; 31 (07) 1103-1107
• 23 Saunders CJ, van der Merwe L, Posthumus M. , et al. Investigation of variants within the COL27A1 and TNC genes and Achilles tendinopathy in two populations. J Orthop Res 2013; 31 (04) 632-637
• 24 Gumina S, Candela V, Passaretti D. , et al. The association between body fat and rotator cuff tear: the influence on rotator cuff tear sizes. J Shoulder Elbow Surg 2014; 23 (11) 1669-1674
• 25 Yamamoto A, Takagishi K, Kobayashi T, Shitara H, Osawa T. Factors involved in the presence of symptoms associated with rotator cuff tears: a comparison of asymptomatic and symptomatic rotator cuff tears in the general population. J Shoulder Elbow Surg 2011; 20 (07) 1133-1137
• 26 Tempelhof S, Rupp S, Seil R. Age-related prevalence of rotator cuff tears in asymptomatic shoulders. J Shoulder Elbow Surg 1999; 8 (04) 296-299

Publikationsverlauf

Eingereicht: 11. September 2018

Angenommen: 26. Februar 2019

Artikel online veröffentlicht:
27. Februar 2020