MOJ ISSN: 2374-6939MOJOR

Orthopedics & Rheumatology
Editorial
Volume 1 Issue 2 - 2014
Unaccustomed Exercise Causes Rhabdomyolysis
Yuri Feito*
Department of Exercise Science and Sport Management, Kennesaw State University, USA
Received: October 31, 2014 | Published: November 01, 2014
*Corresponding author: Yuri Feito, Department of Exercise Science & Sport Management, Kennesaw State University, 520 Parliament Garden Way NW, MD 4104, Bldg. 41, Office 4018, GA 30144, Kennesaw, USA, Tel: 4705787764; Fax: 7704204461; Email: @
Citation: Feito Y (2014) Unaccustomed Exercise Causes Rhabdomyolysis. MOJ Orthop Rheumatol 1(2): 00012. DOI: 10.15406/mojor.2014.01.00012

Not One Type of Exercise Causes Rhabdomyolysis… Any Unaccustomed Exercise Does

Cross Fit TM is a relatively new strength and conditioning program defined as “constantly varied, functional movements, performed at a high intensity”. The goal of the program is to increase “work capacity across broad time and modal domains” [1]. Even though this training modality has been criticized by the main stream media for “high risk of injury” most of these claims have been anecdotal, as recent evidence suggest this training modality is not any more “dangerous” than other exercise programs [2]. One of the biggest criticisms of this training modality has been its association with Rhabdomyolysis, a condition that results in the breakdown of muscle tissue and can result in death [3,4]. However, these claims have not been substantiated by any study looking at the incidence of injury due to Cross Fit participation [2,5,6].

CrossFit® Causes Rhabdomyolysis

The premise that Cross Fit TM causes Rhabdomyolysis suggests a “cause and effect” that has simply not been reported before and it is based on the experience of single individuals, which is far from the number required to make this type of association. Of course, it is unfortunate that anyone would experience an injury due to his or her participation in any type of physical activity. The development of Rhabdomyolysis due to exercise it is possible, but so is sudden cardiac death during an athletic event [7] or during an exercise stress test [8]. The risk of injury, and or death, is inherent to any type of physical activity. Nonetheless, we continue to promote physical activity and exercise to people around the world because the benefits of such activity outweigh the risks for most individuals. The U.S. Department of Health and Human Services encourages all individuals to engage in physical activity of low, moderate or vigorous intensity, suggesting that being sedentary is more “dangerous” than participating in any type of activity [9].

Rhabdomyolysis in the Scientific Literature

If we look to the scientific literature to guide our understanding of this condition, we find several instances where Rhabdomyolysis has occurred as a result of some type of physical activity (exertional Rhabdomyolysis). Inklebarger and colleagues [10] reported the first case of self-induced exertional Rhabdomyolysis in a 63-year-old woman who exercised on a stationary bike a day prior to her emergency room visit. In 2011, Boni and Rabitti [11] reported a case of exertional Rhabdomyolysis after a session of indoor cycling and three other cases have been reported specifically related to resistance training, all of which occurred in a national fitness center chain [12,13]. However, exertional Rhabdomyolysis has also been reported in young adults while performing “less strenuous” activities. A 25-year-old woman required hemodialysis for six-weeks after hiking for hours in the Grand Canyon [14]. A 19-year-old college freshman experience exertional Rhabdomyolysis after playing in an ultimate Frisbee tournament [15]. Therefore, to say that Cross Fit TM causes Rhabdomyolysis is like blaming your favorite running shoe <<ENTER BRAND NAME HERE>> for your shin splints.
Exertional Rhabdomyolysis is caused by a breakdown of muscle fibers due to unaccustomed exercise and it is a life-threatening condition, characterized by muscular pain, muscle weakness, and dark urine. Seeking early treatment is paramount to minimize damage to the kidneys and preventing kidney failure. Even though overexertion may be a significant factor leading to this condition, other factors including dehydration, heat stress, nutritional supplementation, drug use, bacterial or viral infections, genetic conditions (e.g. sickle cell trait), or metabolic defects in the muscle may exacerbate muscle damage, regardless of the exercising intensity [13]. Therefore, individuals, coaches and fitness professionals should be aware of these factors to minimize the risk of this condition regardless of the training modality being performed.

Results

Total 100 patients were included out of which 60 were female and 40 were male patients. Mean age of patients was 31.21±8.52 years. Lower Middle (n=34), Upper Middle (n=33) and Upper Lower socioeconomic classes were more commonly involved as compared to lower (n=8) and upper socioeconomic class (n=3). Majority of patients (n=76) were in healthy weight category. There were (n=9) underweight and (n=15) underweight patients. Majority (n=52) of patients had generalized pain followed by those having lower back pain (n=41), lower limb pain (n=34) and upper limb pain (n=17). A total of (n=11) had upper back pain and (n=9) had hip pain. There were (n=2) patients with pain at other locations. Almost half the patients were vegetarian (n=46). There were (n=54) non-vegetarians but meat consumption at least once a week or more was reported by (n=40) patients only. Although (n=98) patients reported of milk intake yet majority were infrequent milk consumers (n=76). There were only (n=18) patients reporting consumption of at least one glass of milk each day and 4(n=4) who reported consuming more than one glass of milk every day. Almost two third (66%) patients were anemic. Total leukocyte count >10,000/cu mm was recorded in 8 patients. Mean neutrophil, lymphocyte, eosinophil and monocyte count was 67.15±7.49, 27.73±7.09, 3.18±2.60 and 1.95±1.64% respectively. ESR >17 mm/hr was recorded in 57 patients.
All the subjects had 25-(OH) vitamin D2 levels >12.5 n mol/l. Calcium-Phosphorous product was >2.41 n mol/l in 13 (13%). A total of 50 (50%) patients had calcium-phosphorous product in the range of 1.62-2.41 n mol/l and 32 (32%) had Ca-P product in the range of 1.21-1.61 n mol/l. A total of 5 (5%) patients had Ca-P product <1.21 n mol/l. S. Alkaline phosphatase levels were <75 IU/l in 3 (3%) patients only. Total of 22 (22%) had serum ALP levels in range 75-100 IU/l and 75 (75%) had S. ALP levels in the range of 101-201 IU/l. Mean serum parathyroid hormone levels ranged from 21-80 pg/ml with a mean value of 48.35±11.84 pg/ml (Table 3). Radiographs of spine showed normal imaging in 44 cases, areas of rarefaction in 11 cases and decreased density in 45 cases. Similarly pelvis radiographs showed normal density in 47 cases, rarefaction in 8 cases, decreased bone density in 37 cases, Loser’s zone in 4 cases and sclerotic iliac crest in 4 cases. Using McKenna’s criteria as the basis, a total of 20 out of 100 patients with persistent non-specific musculoskeletal pain were found to be confirmed for Osteomalacia.

SN

Variable

No. of Cases

Percentage

1.

25-(OH) Vitamin D levels

 

 

>12.5 nmol/l

100

100.0

2.

Calcium-Phosphorous product

 

 

>2.41 nmol/l

13

13.0

1.62-2.41 nmol/l

50

50.0

1.21-1.611 nmol/l

32

32.0

<1.21 nmol/l

5

5.0

3.

Serum Alkaline phosphatase

 

 

<75 IU/l

3

3.0

75-100 IU/l

22

22.0

101-201 IU/l

75

75.0

4.

Mean S. PTH±SD levels (Range) pg/ml

48.35±11.84 (21-80)

Table 3: Distribution of patients according to vitamin D and other biochemical levels.
In present study, generalized body pain, tenderness near lumbar and/or hip area, dietary scores, hemoglobin level, 25-OH vitamin D, serum calcium, serum phosphorous, serum alkaline phosphatase, serum PTH levels and radiological findings were significantly associated with Osteomalacia. Out of these, generalized body pain, tenderness near lumbar hip area and radiological findings were categorical in nature while dietary score, hemoglobin level, 25-OH vitamin D, serum calcium, serum phosphorous, serum alkaline phosphatase and serum PTH levels were continuous in nature. For the purpose of development of scoring criteria, the continuous variables were converted into categorical variables using receiver operator curve analysis. The criteria for selection of cut-off value were sensitivity above 75%. The cut-off values for diet score, Hb, Vitamin D, S. Ca, S. P, S. ALP and PTH levels were <3, <11.5, <19.23, <8.05, <2.85, >117 and >45.90 respectively (Table 4). For clinical parameters (History and clinical examination) the criteria was 90% sensitive and 63.8% specific.

Variable

Selected cut-off

Independent Efficacy

Sensitivity

Specificity

Diet score

<3

80

65

Hb (gm/dl)

<11.5

75

62.5

Vitamin D (ng/ml)

<19.23

90

70.0

S. Ca (mg/dl)

<8.05

80

50

S. P (mg/dl)

<2.85

75

62.5

S. ALP (IU/L)

>117

85

61.2

PTH (pg/ml)

>45.90

75

48.7

Table 4: Cut-off variables for variables found to be significantly associated with Osteomalacia.
However, it had a very low PPV (positive predictive value) (38.3%) and a high NPV (negative predictive value) (96.2%). The overall efficiency (Youden’s Index) was 53.8% only. For laboratory parameters (hematological and biochemical criteria) the criteria was 95% sensitive, 55% specific, had a PPV of 34.5% and a NPV of 97.8%. Overall efficiency of the criteria was 50%. Similarly for radiological parameter the criteria were 80% sensitive and 63.75% specific with a very low PPV (35.56%) and a high NPV (92.73%). The overall efficiency (Youden’s Index) was 43.75% only. Vitamin D parameter showed a sensitivity of 75%, specificity of 93.8%, PPV 75% and NPV 93.8% with an accuracy of 68.8% (Table 5).
After binary regression, we observed that only generalized pain at presentation and vitamin D level of <19.23ng/ml was significantly associated with outcome. On evaluating the combination of presence of these criteria we observed it to be 75% sensitive and 93.8% specific with a PPV of 75% and NPV of 93.8% and an accuracy of 68.8%.

 

Clinical Parameter

Laboratory Parameter

Radiological Parameter

Vitamin D Parameter

Positive

Negative

Total

Positive

Negative

Total

Positive

Negative

Total

Positive

Negative

Total

OSTEOMALACIA

Positive

18

02

20

19

01

20

16

04

20

15

05

20

Negative

29

51

80

36

44

80

29

51

80

5

75

 

Total

47

53

100

55

45

`100

45

55

100

20

80

 100

Sensitivity

Specificity

PPV

NPV

YI

90%

63.8%

38.3%

96.2%

53.8%

95%

55%

34.5%

97.8%

50%

80%

63.75%

35.56%

92.73%

43.75%

75%

93.8%

75%

93.8%

68.8%

Table 5: Comparison of various parameters in diagnosis of Osteomalacia.

Discussion

On evaluating the association between age and Osteomalacia, the association was not found to be significant (p=0.467). Like persistent non-specific musculoskeletal pain, Osteomalacia has also been reported to be prevalent in all age groups. The mean age of patients in the present study was 31.21±8.52 years (range: 18 to 65 years), [11] too did not find any association between age and Osteomalacia and did not include age as a component of diagnostic index developed by them. Similar results of age and Osteomalacia was found in other study [12]. In their study among adolescents (10-16 years) reported the mean age of patients to be 13.2 years only.
In present study, the prevalence was higher in females (65%) as compared to males (35%) yet the association could not be established statistically (p=0.610). Although prevalence of Osteomalacia has been reported to be higher in females with a female to male ratio being as high as 11.33:1 [2] to 5:1 [13]. Majority of our patients were from middle (lower middle and upper middle) socioeconomic strata. Socio-economic status, a measure of deprivation, is typically classified by examination of factors such as home ownership, levels of unemployment, and education. There is an inverse relationship between socio-economic status and the prevalence of both acute and chronic pain [14-17]. However, contrary to these reports, in present study, lower middle and upper middle class was more widely affected. A possible explanation for this could be association of chronic wide spread pain with physical inactivity [18].
In present study, majority (52%) of patients had generalized pain followed by those having lower back pain (41%), lower limb pain (34%) and upper limb pain (17%). A total of 11 had upper back pain and 9 had hip pain. There were 2 patients with pain at other locations. Among patients not reporting with generalized body pain, except for 1 patient, all the patients had pain at one or more locations. More than half the patients not reporting generalized pain had involvement of three or more sites. These findings are in concordance with the observations of [19] who also reported that chronic musculoskeletal pain is rarely present in a single body site.
In present study, majority of patients were anemic (66%). Thus, indicating a high prevalence of nutritional deficiency. Hypovitaminosis D has often been seen to be manifested in combination with other nutritional deficiencies like anemia [20]. In present study, we evaluated serum 25(OH)-vitamin D levels [11] using the criteria of and found that all the patients had vitamin D levels more than 12.5 n mol/l. However, using the criteria proposed by Holick [21] who proposed a normal range of 50-140 n mol/l, we found exactly half the patients (n=50) to be having 25-(OH) Vitamin D3 levels to be less than 50nmol/l, thus indicating a high prevalence of Hypovitaminosis D in the study subjects. A number of researchers have attributed Hypovitaminosis D to be the cause attributable to persistent non-specific musculoskeletal pain [22,23]. However, using the criteria all the patients were seen to be having low Ca-P product and raised Alkaline Phosphatase levels [11]. Using normal reference range of PTH to be 0-40 IU/L, as many as 74 cases had values above 40 IU/L.
Using McKenna’s criteria, a total of 20 out of 100 patients with persistent non-specific musculoskeletal pain were found to be confirmed for Osteomalacia. Osteomalacia has been reported to be a common reason for persistent non-specific muscular pain [22] especially in cases with Hypovitaminosis D. In present study, we had a high prevalence of hypovitaminosis D and it could be attributed to the high prevalence of Osteomalacia in these patients. In our study, tenderness near lumbar/hip area was found to be significantly associated with Osteomalacia (p=0.021). All cases were able to perform their routine tasks and were fully ambulatory, thus indicating a mild form of disease.
In present study, vegetarian or infrequent non-vegetarian diet and irregular or no milk consumption were found to be associated with Osteomalacia (p<0.05). Mean dietary scores were significantly lower in cases of Osteomalacia (2.25±0.79) as compared to those without Osteomalacia (3.9±1.77) (p<0.001). A clear-cut relationship between nutritional deficiency and Osteomalacia has also been shown by others [24-27]. Evaluation of hematogical parameters showed that except for mean hemoglobin levels statistically no significant difference was observed between two groups with respect to any of the hematological parameters (p<0.001).
Vitamin D deficiency is the most commonly reported cause of Osteomalacia and is reported in almost all the diagnostic work ups for Osteomalacia. According to Osteomalacia [27] is an end-stage bone disease of chronic and severe vitamin D or phosphate depletion of any cause. For the purpose of validation, three sets of criteria were evolved – clinical and dietary criteria, hematological and biochemical criteria and radiological criteria. Three criteria were evolved as we focused on developing simplified criteria which can have accuracy level close to that of McKenna’s Diagnostic Index [11].
On evaluating the clinical and dietary criteria, it was found to be 90% sensitive and 63.8% specific. However, it had a very low PPV of 38.3% and a high negative predictive value of 96.2%. The overall accuracy (Youden’s Index) was 53.8% only. The clinical criterion is easy to be used and can decrease the burden of sophisticated investigations by around 50% and hence can be used as a pre-hospital / self-assessment criteria with ample sensitivity (90%). Hematological and biochemical criteria was based on estimation of hemoglobin, Vitamin D, serum Ca, S. P, S. ALP and PTH levels, thus including a spectrum of diagnostic tests which helped it to yield a highly sensitive criteria (95%) but owing to high prevalence of anemia in Indian population resulted in a less specific outcome (55%) and made its positive predictive value highly compromised (34.5%). The radiological criteria independently too had the limitation of low specificity and had specificity similar to clinical and dietary criteria (63.8%) but had a sensitivity lower than the other two criteria.
In order to improve the diagnostic efficacy of our criteria, we suggest the use of a combined criteria of two factors- generalized non-specific persistent pain on presentation and vitamin D levels <19.23ng/ml and found it to be highly specific (93.8%). If all the cases diagnosed as positive by clinical and dietary criteria are also included in these criteria then it turns out of be 85% specific.
This modified two-component criteria was 85% sensitive, 93.8% specific had a positive predictive value of 77.3% and a negative predictive value of 96.2% and diagnostic efficacy of 81.2%. (Table 6). The criteria developed in present study was developed in a specific population and was validated against an already existing non-invasive diagnostic criteria, however, its efficacy against biopsy proven cases of Osteomalacia needs further evaluation apart from its validation in different population groups. If the proposed criteria emerges as a useful utility against both biopsy proven Osteomalacia cases and is applicable in various populations then it can be used as a simplified diagnostic tool with adequate accuracy, however, even in its present form it is a useful criteria for assessment of Osteomalacia and can be used in a low resource setting.

References

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  11. Boni R, Rabitti PG (2011) Spinning-induced rhabdomyolysis: importance of MRI for patient's outcome a case report. Reumatismo 63(1): 44-48.
  12. Casares P, Marull J (2008) Over a millon Creatine Kinase due to a heavy work-out: A case report. Cases J 1(1): 173.
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Generalized Body Pain + Vitamin D <19.23 ng/ml or Positive in Clinical Criteria

Osteomalacia

Total

Positive

Suspect/ Negative

Positive

17

5

22

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