A 29-year-old woman of Moroccan origin was admitted to the Department of Gastroenterology because of refractory celiac disease and suspected osteomalacia. Her medical history revealed growth retardation and iron deficiency from the age of 6 and the diagnosis of celiac disease at the age of 17. At the age of 27, there was an ongoing symptomatic celiac disease despite a gluten-free diet. On admittance to our hospital, the patient complained of progressive bone pain over the last 2 years, mainly located in the ribs, spine, hips, and shoulders. She also had severe difficulty with walking and was in fact wheelchair-bound. She was short of breath during normal daily activities and had lost 15 kg in 3 years. She had a regular menstrual cycle, and her menarche was at 17 years of age. She had neither abdominal complaints nor diarrhea. On physical examination, she was pale. Her body height was 148 cm (previously 156 cm) and her weight, 38 kg. She had bad dentition, and the back showed a scoliosis and pronounced thoracic kyphosis with thoracic and lumbar percussion pain. Pelvis and shoulders also were painful on touching. There was muscle atrophy and symmetrical loss of proximal muscle strength.
Laboratory evaluation at presentation showed hypocalcemia, low serum phosphate, high alkaline phosphatase, and a serum 25-hydroxyvitamin D (25(OH)D) level below the detection limit, as shown in Table . The serum parathyroid hormone level was strongly elevated. Furthermore, the patient had low serum vitamin A (0.9 μmol/L; normal, 1.2–3.0), vitamin B1 (78 nmol/L; normal, 80–160), and vitamin B6 (6 nmol/L; normal, 13–80) levels. Her serum folic acid level (30.7 nmol/L; normal, >6) and serum vitamin B12 level were normal (150 pmol/L; normal, 10–700), and there were no signs of iron deficiency. At that moment, she was using the following medications prescribed in the referring hospital: calcium carbonate 1,000 mg twice daily, naproxen 500 mg twice daily, pantoprazole 20 mg once daily, tramadol 50 mg twice daily, ferrioxidesaccharaat 200 mg once a week (intravenous), alfacalcidol 0.5 μg once daily (intravenous), alendronic acid 70 mg once a week, and folic acid 5 mg once daily (intravenous).
Results of laboratory evaluation, BMD measurement and histomorphometry
Radiographs of the thoracic and lumbar spines had a milk glass appearance and were not sharply delineated. The lumbar vertebrae had a biconcave codfish appearance (Fig. ) Bone mineral density measurement (Hologic) showed extremely low absolute values and T-scores (Table ). A skeletal scintigraphy with technetium-99 M showed a diffusely elevated uptake in sternum, mandible, and long bones and an absent kidney sign. There were also multiple symmetric focal lesions with enhanced uptake in the ribs, compatible with rib fractures or fissures (Fig. ). To confirm the clinical diagnosis of osteomalacia in this patient with severe refractory celiac disease and extremely low BMD, a bone biopsy was obtained from the right iliac crest (Fig. ). This biopsy showed a relative osteoid volume of more than 70% and signs of increased bone turnover compatible with secondary hyperparathyroidism. The osteoid was covered with high numbers of active osteoblasts, and resorption lacunae were filled with multinucleated osteoclasts. Peri-trabecular fibrosis was also observed. The trabecular bone volume (BV/TV) was normal, i.e., not compatible with osteoporosis.
Radiographs, lateral view, of the lower thoracic (a) and lumbar vertebrae (b). Thoracic vertebrae are blurred and lumbar vertebrae show codfish appearance
Bone scintigraphy; Whole body, anterior view (a) and detail of the ribs, lateral view (b). Hot spots may indicate pseudofractures or fissures
This Moroccan young woman with refractory celiac disease had a very severe osteomalacia with an extremely low bone mineral density due to a severe vitamin D deficiency. Treatment with alendronic acid was discontinued, and the patient was treated during 14 days with intravenous calcium glubionate up to 8,250 mg (540 mg or 13.5 mmol Ca++) daily and oral cholecalciferol 10,000 IU daily. After these 14 days, her medication consisted of 7 g of calcium carbonate and 1,200 IU cholecalciferol daily in an outpatient setting. After the intravenous treatment, the serum 25(OH)D level increased to 56 nmol/L, and the symptoms of the patient rapidly improved; the bone pain decreased, muscle strength and physical performance improved markedly, and she was able to walk unassisted.
After initiating oral treatment with calcium and lowering the cholecalciferol dose, there was a gradual decline of 25(OH)D, and we had to increase the oral dose of cholecalciferol to 10,000 IU a day. Questioning revealed gluten exposure and patient was given advice repeatedly on how to maintain a strict gluten-free diet. After raising the oral dose of cholecalciferol, the serum 25(OH)D level increased to 34 nmol/L, and the 1,25(OH)vitamin D to >250 pmol/L. Bone mineral density measurement 5 1/2 months after initiation of therapy showed a significant increase at the lumbar spine (L1–L4) and hip, 0.44 g/cm2 (T-score, −5.5) and 0.22 g/cm2 (T-score, −5.9), respectively. Further follow-up of this patient was not possible because she did not respond to multiple invitations to visit our outpatient clinic.