Article

Thoracic spine fracture in the course of severe nocturnal hypoglycemia in young patients with type 1 diabetes mellitus—the role of low bone mineral density

Unlabelled imageAmerican Journal of Emergency Medicine 32 (2014) 816.e5-816.e7

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American Journal of Emergency Medicine

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Case Report

Thoracic spine fracture in the course of severe nocturnal hypoglycemia in young patients with type 1 diabetes mellitus–the role of low bone mineral density?

Abstract

Thus far, only a few spine fracture cases related to severe nocturnal hypoglycemia in type 1 diabetes patients have been reported. Due to the relatively young age of these subjects, osteoporosis was not taken into consideration and bone mineral density was not assessed.

We report three type 1 diabetes cases in young patients with durations of 2, 4, and 19 years. These patients had severe hypoglycemic attacks during night sleep with subsequent compres- sion thoracic vertebrae fractures. Laboratory parameters for diabetes control, calcium, phosphate metabolism and celiac-specific antibodies were assessed. Moreover, kidney, thyroid, and parathyroid gland functions were also measured. Bone mineral density was assessed by dual energy x-ray absorptiometry.

lumbar spine x-ray absorptiometry revealed very low bone mineral density in all three patients. In all subjects, metabolic control was good, no chronic diabetes complications were found and other laboratory parameters were within a normal range.

For the first time, it was demonstrated that low bone mineral density in young type 1 diabetes patients may contribute to an increased compression fracture risk of the dorsal spine during severe nocturnal hypoglycemia courses. The possibility of osteoporosis in young patients with short diabetes durations suggests it might be advisable to perform bone mineral density testing during diabetes diagnoses. Spinal pain occurrences in young patients after severe nocturnal hypoglycemia should be investigated using procedures for the diagnosis of vertebral compression fracture, even if there is no evident trauma.

Nocturnal hypoglycemic fits are very frequent among type 1 diabetes mellitus patients. Severe hypoglycemic episodes associated with loss of consciousness are sometimes accompanied by tonic muscle contractions and convulsions that resemble an epileptic attack. The most commonly reported musculoskeletal injuries related to Epileptic seizures involve thoracic spine compression fractures, Proximal humerus and femur fractures as well as Shoulder joint dislocations [1-4]. The enormous mechanical forces that act on the musculoskeletal system as a result of uncontrolled large muscle group contractions cause these injuries. In type 1 diabetes mellitus (DM1) patients, musculoskeletal system injuries related to severe hypogly- cemic attacks that occur through a similar mechanism are rarely taken into consideration. So far, only a few spine fracture cases related to hypoglycemic fits have been reported, and all of them were

? Conflict of interest: The authors have explicitly stated that there are no conflicts of interest in connection with this article.

compression fractures in men [5,6]. Due to the relatively young age of these patients, osteoporosis was not taken into consideration and bone mineral density (BMD) was not assessed.

Long duration diabetes mellitus is known to precipitate osteopenia and osteoporosis development, although the mechanisms leading to these conditions are complex and unclear. Low BMD may be observed in DM1, while in type 2 diabetes, the BMD is similar to that of non- diabetic subjects [7]. Both types of diabetes, however, are associated with a higher fracture risk [7,8]. The pathogenetic mechanisms responsible for low BMD in DM1 are not fully understood but may include insufficient anabolic insulin and insulin growth factor (IGF-1 and IGF-2) effects, reduced renal function, microangiopathy, higher advanced glycation end product concentrations in collagen and inflammation [8]. Patients with a recent onset of DM1 (childhood, adolescence), may have impaired bone formation and lower peak bone mass. The role of metabolic control in osteopenia is not well established. According to some studies, lower BMD in DM1 patients is not linked to poor long-term Glycemic control; however, others have observed that reduced bone status was significantly marked in subjects with higher long-term hemoglobin A1c [7,9,10].

Below, we present a report of 3 young DM1 patients who suffered thoracic vertebrae fractures due to a severe hypoglycemic nocturnal episode. The described events were observed in patients that attended the Department of Diabetology and Internal Diseases outpatient clinic in Szczecin, Poland (period 1998-2012). Notably, none of the patients were known to have a history of epilepsy. Additionally, all three subjects were eugonadal and their Nutritional status was normal. The laboratory diabetes control, calcium and phosphate metabolism, kidney, thyroid and parathyroid gland function parameters were measured and serological celiac disease screening was performed (Table). BMD was assessed by dual energy X-ray absorptiometry (DEXA). All three patients gave their written consent for the publication of their medical history.

Case 1 included a 21-year-old man with DM1, who was diagnosed at the age of 19 and had a very unstable disease course, which included several hospitalizations due to ketoacidosis or Severe hypoglycemia. The patient experienced a severe hypoglycemic episode during night sleep. Any injury was noted; however, it is unknown if he had any seizures. After the patient woke up, he was transported to a hospital due to severe vertebral pain. An x-ray image demonstrated a Th7 vertebra compression fracture with 35% anterior wedging and a mild Th8 vertebra biconcave fracture (Fig. A). A DEXA of the lumbar spine revealed low BMD, including a -2.4 T-score and a

-2.3 Z-score for the L1-L4 vertebrae. Gastroscopy did not demon- strate any evidence of gastrointestinal disease.

0735-6757/(C) 2014

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Table

Characteristics of type 1 diabetes patients with compression spine fracture that occurred in the course of severe nocturnal hypoglycaemia

Patient 1.

Patient 2.

Patient 3.

Sex

Male

Female

Male

Age at the moment

21

19

30

of fracture (years)

Diabetes duration at the time of

2

4

19

fracture (years) BMI (kg/m2)

21.7

19.3

23.0

HbA1c

(%)

6.4

6.7

7.4

(mmol/mol)

46

50

57

Insulin dose (IU/kg)

0.59

0.83

0.56

insulin therapy algorithm

Human rapid insulin (3x) and

Rapid insulin analogue (3x) and

Human rapid insulin (3x) and

insulin NPH (1x)

insulin NPH (2x)

insulin NPH (2x)

Serum creatinine (umol/L)

70.7 (N: 61.9-106.1)

53.9 (N: 58.3-96.4)

82.2 (N: 71.6-127.3)

GFR (mL/min)

(Cockcroft-Gault formula, N: N90)

143

151

120

Total calcium

NA

2.25

2.42

(mmol/L)

(N: 2.15-2.55)

Ionized calcium (mmol/L)

1.25

1.16

1.19

(N: 1.05-1.35)

Inorganic phosphorus

1.3

1.1

0.8

(mmol/L)

(N: 0.87-1.45)

Alkaline phosphatase (U/L)

79 (N: 40-129)

114 (N: 32-104)

148 (N: 30-120)

PTH

38.75

29.7

17.83

(pg/mL)

(N: 15.0-65.0)

TSH (uIU/mL)

1.98 (N: 0.27-4.2)

1.68 (N: 0.4-4.0)

1.83 (N: 0.4-4.0)

Celiac-specific antibodies (IgA):

Anti-transglutaminase

Negative

Negative

Negative

Anti-endomysium

Negative

Negative

Negative

Anti-gliadin

Negative

Negative

Negative

BMI, body mass index; HbA1c, glycated haemoglobin, GFR, glomerular filtration rate; PTH, parathormone; TSH, thyroid stimulating hormone.

Case 2 included a 21-year-old woman who was diagnosed with DM1 at the age of 15 and had a history of frequent nocturnal hypo- glycemic episodes. She was diagnosed with mild hyperthyroidism at age 19 and was treated successfully with thyreostatic drugs for 1 year. At the same age, the patient lost consciousness while lying in bed in the early morning hours (her capillary blood glucose was 1.1 mmol/L). Notably, a witness to the event did not see any convulsions. After receiving intravenous glucose, she regained consciousness and com- plained of severe back pain. Multiple rehabilitation sessions were con- ducted and anti-inflammatory or analgesic treatments were administered, but without any x-ray Diagnostic procedures. After 11 months of persistent pain in the thoraco-lumbar spine, imaging studies (x-ray and MRI) were performed and demonstrated an inveterate Th12 vertebra wedge fracture (Fig. B). The patient underwent a surgical

spine fixation. At the age of 21, lumbar spine and femur DEXAs demonstrated significantly reduced BMD, whereby a -3.1 T-score and a -3.1 Z-score for the L2-L4 vertebrae and a -2.7 T-score and a -2.8 Z-score for the femur were observed. No significant abnormalities were found in the physical examination or laboratory tests.

Case 3 included a 30-year-old man who regularly performed hard manual labor work, was diagnosed with DM1 at 11 years of age and had a history of frequent hyperglycemic and hypoglycemic episodes. This patient was found lying unconscious in bed by family members. Additionally, highly increased muscle tension and tonic contractions, without accompanying convulsions, were observed in this patient. A capillary blood glucose level of 1.1 mmol/L was measured. After glucagon administration, the patient regained consciousness and was brought to the hospital. The patient complained of pain in the upper

A

B

C

Fig. The compression spine factures of the young type 1 diabetes subjects.

L. Majkowska et al. / American Journal of Emergency Medicine 32 (2014) 816.e5816.e7 816.e7

lumbar spine region, and limited mobility and tenderness of this region were found; however, evidence of other chronic diseases or diabetic complications was not found. Imaging studies, including X-ray and CT scans, demonstrated concave fractures in the upper Th11 and Th12 vertebral body endplates (Fig. C). A lumbar spine DEXA revealed osteopenia with a -2.2 T-score and a -2.0 Z-score in the L1-L4 vertebrae.

Vertebral fractures following epileptic fits are typically compres- sion fractures that occur in the thoracic region, usually without neurological deficit. They are caused by strong paraspinal muscle contractions during tonic-clonic seizures. A similar mechanism may cause vertebral bone fractures in subjects who do not suffer from epilepsy, but develop seizures or body tonic contractions, as reported in previous cases, including those of a 48-year-old man with severe hypokalemia and Cushing’s syndrome and a 16-year-old girl with tetany related to DiGeorge syndrome [11,12].

Severe hypoglycemia patients may lose consciousness and develop increased muscle tension, sometimes with seizures or body tonic contractions. Previously reported cases of non-traumatic spine fractures were related to hypoglycemic fits occurring in men aged 30-50 years and usually with long diabetes durations [5,6]. All of these injuries were sustained during night sleep. In some unwitnessed cases, convulsions preceding vertebral fractures could not be confirmed. The pathomechanism of fractures and their association with higher muscle mass may explain the exclusive occurrence of this complication in males.

Fractures occurring without any trauma suggest previous bone fragility due to osteoporosis or the presence of another illness. Vertebral fractures are the earliest and most common osteoporotic fractures. Low BMD, demonstrated by bone densitometry, was present in all three patients despite their young age and was most likely a significant pathogenetic factor here. Characteristic clinical vertebral fracture symptoms, such as back pain and functional impairments, appeared just after the hypoglycemic attacks. In two of our patients, a 21-year-old man and a woman, low BMD was found despite their young age, short diabetes durations, good metabolic control and lack of any diabetic complications. Both subjects were characterized by a relatively low body mass index, which can be associated with decreased BMD [13]. Osteoporosis in the woman could have been caused by hyperthyroidism in the past. The very low BMD found in the 30-year-old man with a long diabetes dura- tion cannot be assigned to nephropathy, other microangiopathy or the presence of another clinically overt disease. In this case, the early onset and long diabetes duration could have played a role in the bone loss.

The pathogenesis of low BMD in the three reported patients, especially in both men, remains unclear. The known fact of the common coexistence of DM1 and celiac disease could suggest that osteoporosis was of this etiology [14,15]. In the majority of cases, celiac disease is already present at diabetes onset and is mostly asymptom- atic and undetected with no signs of overt malnutrition [15]. The medical histories, physical examinations and serological tests of our patients did not indicate the presence of celiac disease; however, a mild form of this disease could not be ruled out in their childhoods and early adolescence when their maximum bone mass was built.

To our knowledge, we have demonstrated for the first time that low BMD can be a significant cause of spine fracture without

coexisting trauma in young DM1 patients who have suffered severe nocturnal hypoglycemia. Additionally, we have also described this complication in a young woman with DM1 for the first time. The possibility of osteoporosis in young patients with short DM1 dura- tions without vascular complications or other clinically overt coex- isting diseases suggests it might be advisable to perform BMD tests at diabetes diagnosis and then repeat them regularly. Spinal pain in young DM1 patients after loss of consciousness due to hypoglyce- mia should be investigated using procedures to diagnose compres- sive bone fracture even if the patients did not fall and there was no evident trauma.

Liliana Majkowska, MD, PhD

Ewa Walilko, MD Piotr Moleda, MD, PhD

Department of Diabetology and Internal Diseases

Pomeranian Medical University

Szczecin, Poland

Andrzej Bohatyrewicz, MD, PhD

Department of Orthopedics Traumatology and Musculoskeletal Oncology Pomeranian Medical University

Szczecin, Poland E-mail address: [email protected]

http://dx.doi.org/10.1016/j.ajem.2013.12.055

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