Bone Alkaline Phosphatase (BALP), Elevated

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What Is Elevated Bone Alkaline Phosphatase?

Elevated bone alkaline phosphatase (BALP) is a laboratory result that indicates an abnormal blood level of this bone enzyme.

A bone alkaline phosphatase blood level is one of the most frequently used biochemical markers of bone formation.

Q: Why is the purpose of  bone alkaline phosphatase?

A: Bone alkaline phosphatase is produced by bone cells called osteoclasts in normal bone maintenance for the purpose of breaking down old or damaged bone so that other bone cells called osteoblasts can fill in the excavated areas with new bone. This process keeps bone stong and healthy.

Elevated bone alkaline phosphatase shows that more bone is being broken down than is being replaced. It can be caused by hyperparathyroidism, bone tumors from cancer, and malnutrition.

What Is Elevated Bone Alkaline Phosphatase (BALP) In Celiac Disease and/or Gluten Sensitivity?

• Relationship between elevated bone alkaline phosphatase and celiac disease. Elevated bone alkaline phosphatase is a classic feature of calcium malabsorption in untreated celiac disease that is characterized by altered bone mineral density, or bone thinning, seen in osteopenia and osteoporosis.
• Relationship between elevated bone alkaline phosphatase and bone loss. Determination of bone alkaline phosphatase activity can predict bone loss in secondary osteoporosis associated with celiac disease, and is helpful in diagnosing celiac disease and monitoring anti-resorptive therapy such as calcium supplementation.1
• Relationship between elevated bone alkaline phosphatase and osteomalacia. Bone softening results in osteomalacia in adults and rickets in children with vitamin D deficiency causing calcium deficiency.
• Relationship between elevated bone alkaline phosphatase and hyper-parathyroidism. Hyperparathyroidism develops  from chronic calcium deficiency. Excessive parathyroid hormone is released in the effort to supply calcium to the body by releasing it from bone through the action of alkaline phosphatase. Unfortunately, this process of removing calcium weakens bone.
• Relationship between elevated bone alkaline phosphatase and gluten free diet. In the study by Zanchi et al below, calcium metabolism defects were found to be common in untreated children with celiac disease, and they returned to normal after gluten-free diet.2

How Prevalent Is Elevated Bone Alkaline Phosphatase In Celiac Disease and/or Gluten Sensitivity?

An elevated level of BALP is a common serology result in patients with untreated celiac disease.3

67% of patients who were diagnosed with celiac disease at a hospital endocrinology department had elevated BALP.4

What Are The Symptoms Of Elevated Bone Alkaline Phosphatase?

Elevated bone alkaline phosphatase is marked by these symptoms:

• Bone pain.
• Bone weakness causing brittleness subject to breaking.
• Bone softening causing bone deformity seen in rickets (children) and osteomalacia (adults).

How Does Elevated Bone Alkaline Phosphatase Develop In Celiac Disease and/or Gluten Sensitivity?

• Elevated bone alkaline phosphatase results from calcium malabsorption in celiac disease.5
• Decreased absorption of calcium causes the parathyroid glands in order to maintain normal calcium levels to secrete parathormone. Parathormone activates bone cells called osteoclasts to secrete alkaline phosphatase which breaks down bone and releases calcium.

Does Elevated Bone Alkaline Phosphatase Respond To Gluten-Free Diet?

Yes. Celiac disease-related elevated BALP normalizes on gluten free diet containing adequate calcium.6

6 Steps To Improve Elevated Bone Alkaline Phosphatase Blood Level:

• 1Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

• 2 Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

• 3 Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• 4 Manage Your Medications Safely:

• 5Nutritional Supplements To Help Correct Deficiencies:

• 6Manage Natural Remedies: 

What Do Medical Research Studies Tell About Elevated BALP In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Endocrine manifestations of celiac disease.” This study investigating the prevalence of endocrinopathies in 36 patients who were diagnosed with celiac disease at a hospital endocrinology department found a prevalence of elevated alkaline phosphatase in 67%.

Other abnormalities included short stature (58%), delayed puberty (31%), low calcium (22%), X-rays suggestive of osteomalacia or rickets (8%), carpopedal spasm (6%), and night blindness (6%). Anti-TPO antibody positivity was found in 53%, hypothyroidism in 28%, subclinical hypothyroidism in 17%, and type-1 DM in 25% of the patients. A total of 14% patients had no GI symptoms.9

“Bone metabolism in celiac disease.” This study investigating the prevalence of both calcium metabolism alterations and bone defects in 54 untreated children with celiac disease (mean age, 7 years), found that calcium metabolism defects are common in untreated children with celiac disease, and they returned to normal after gluten-free diet.

Serum concentration of calcium, magnesium, 25(OH)vitamin D3, alkaline phosphatase, and parathyroid hormone (PTH) of patients with celiac disease was compared with those of 60 healthy children. Children with celiac disease with 2 laboratory alterations further underwent DEXA examination (bone density test), which was evaluated after 6 months of a gluten-free diet. The calcium and the 25(OH)vitamin D3 levels were lower in children with celiac disease than in control subjects, and the PTH level was higher in children with celiac disease than in control subjects. Hyperparathyroidism was found in 29 children with celiac disease. Twenty patients tested positive for 2 laboratory alterations, and 10 of them were osteopenic. After 6 months of a gluten-free diet calcium, 25(OH)vit.D3 and PTH levels normalized, with the improvement of bone mineral density.10

“Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake.” This study investigating calcium absorption and bone mineral density (BMD) after a prolonged, over 4 years, treatment with a Gluten Free Diet demonstrated significant inverse correlations between 1) serum parathyroid hormone (PTH) and femoral neck or total body BMD, 2) PTH and duration of Gluten Free Diet, and 3) fractional calcium absorption and alkaline phosphatase. Increased calcium intake could potentially compensate for the reduced fractional calcium intake but may not normalize the BMD. Serum calcium and serum 25(OH)D concentrations did not differ from controls. In addition, the inverse correlation between PTH and time following treatment is suggestive of a continuing long-term benefit of gluten withdrawal on bone metabolism in celiac disease patients.6

“Osteomalacia due to vitamin D depletion: a neglected consequence of intestinal malabsorption.” This study investigating the belief that vitamin D depletion is rare in the United States shows that osteomalacia due to vitamin D depletion appears not to be suspected or diagnosed promptly in susceptible patients, perhaps because their physicians were not sufficiently aware of this condition. Researchers present a series of patients with histologically verified osteomalacia due to vitamin D depletion to emphasize the need for more careful and systematic surveillance of patients at risk of this metabolic bone disease.

Between 1989 and 1994, 17 patients with osteomalacia due to vitamin D depletion were seen in the Bone and Mineral Division of Henry Ford Health System, Detroit. All patients had a transiliac bone biopsy. Biochemical indexes of vitamin D nutritional status, parathyroid function, markers of bone turnover, and bone mineral density were assessed at the time of bone biopsy. The duration of symptoms, the lag between the cause of vitamin D depletion and the development of symptoms, and the x-ray findings were recorded. Osteomalacia was suspected by the referring physician in only 4 of the 17 patients, although a gastrointestinal disorder that can lead to vitamin D depletion was present in every patient. Thirteen of the patients had sustained at least one osteoporotic fracture (wrist, spine, or hip), and most had low appendicular and axial bone mineral density. All patients had one or more biochemical abnormalities consistent with vitamin D depletion. In 4 patients, a progressive rise in the serum alkaline phosphatase level was recorded but was not investigated until the patient presented with bone pain, muscle weakness, or fracture.11

CASE REPORT SUMMARIES

“Carpopedal spasm in an elderly man: an unusual presentation of celiac disease.” This case report describes diagnosis of celiac disease in a 68-year-old single Caucasian man admitted to the hospital with a 24-hour history of carpopedal spasm of both hands. Apart from generalized weakness, he reported no other symptoms. Physical examination revealed carpopedal spasm, clubbing of fingers and cachexia. This patient was found to have several unusual features of celiac disease, including negative tTG-antibodies despite partial and subtotal villous atrophy of the duodenum, elevated alkaline phosphatase, severe hypocalcemia, electrolyte disturbances, and minimal gastrointestinal symptoms.

Blood tests showed severe hypocalcemia, with a total serum calcium of 1.06 mmol/L (normal range [NR] 2.05-2.55 mmol/L). He also had low serum potassium (2.8 mmol/L; NR 3.5-5.5 mmol/L) and magnesium (0.36 mmol/L; NR 0.65-1.05 mmol/L). Other significant results included hemoglobin 10.6 g/dL (NR 13-18 g/dL), mean corpuscular volume 98.1 fl (NR 82-98 fl), vitamin B12 157 ng/L (NR > 165 ng/L), folate 2.8 g/L (NR 3.1-17.5 μg/L), ferritin 252 μg/L (NR 30-250 μg/L), prothrombin time 20 s (NR 11-14 s), thyroid stimulating hormone 0.87 mu/L (NR 0.35-4.5 mu/L), phosphate 0.57 mmol/L (NR 0.8-1.45 mmol/L), albumin 32 g/L (NR 34-48 g/L) and alkaline phosphatase 313 IU/L (NR 47-141 IU/L).  Subsequent results revealed vitamin D deficiency with a low serum 25-OH vitamin D of < 7 μg/L (NR 7-40 μg/L), a low 24-hour urinary calcium excretion of 0.9 mmol (NR 2.5-7.5 mmol) and a raised serum parathyroid hormone of 22.7 pmol/L (NR 1.6-6.9 pmol/L).

Serology for tissue transglutaminase (tTG) antibodies was negative, and a serum IgA level of 4.95 g/L (NR 0.8-4.0 g/L) excluded selective IgA deficiency.

Barium meal and follow through showed dilated proximal bowel loops and absence of normal feathery pattern of the jejunum, features suggestive of a malabsorptive state. Upper gastroscopic examination was normal; however, the duodenal biopsy showed partial and subtotal villous atrophy with increased intra-epithelial lymphocyte infiltration, consistent with the diagnosis of celiac disease.12

“Disabling osteomalacic myopathy as the only presenting feature of coeliac disease.” This case report describes diagnosing celiac disease in a 59-year-old woman who presented with a 3-month history of bilateral, proximal lower-limb weakness associated with disabling pain that rendered her wheelchair-bound. There were no gastrointestinal symptoms. Clinical examination showed evidence of bilateral, proximal muscle atrophy and weakness in the lower limbs.

Low serum calcium and raised serum alkaline phosphatase, coupled with radiological findings, led to the diagnosis of osteomalacia. Subsequent gastroscopy and duodenal biopsy confirmed a diagnosis of coeliac disease. With adherence to a gluten-free diet, the patient’s condition remarkably improved within 3 months and she could walk pain-free using a stick. Osteomalacia and myopathy may rarely be the initial and primary presentations of coeliac disease. There are very few reports of osteomalacia as the only presentation of coeliac disease and no reports that describe such a dramatic recovery 3 months after commencing a gluten-free diet.13

1. Ambroszkiewicz J, Gajewska J, Laskowska-Klita T. Bone alkaline phosphatase: characteristic and its clinical applications. Medycyna Wieku Rozwojowego. Apr-Jun 2002;6(2):99-110. [↩]
2. Zanchi C, Di Leo G, Ronfani L, Martelossi S, Not T, Ventura A. Bone metabolism in celiac disease. J Pediatr. 2008 Aug;153(2):262-5. doi: 10.1016/j.jpeds.2008.03.003 [↩]
3. Ambroszkiewicz J, Gajewska J, Laskowska-Klita T. Bone alkaline phosphatase: characteristic and its clinical applications. Medycyna Wieku Rozwojowego. Apr-Jun 2002;6(2):99-110. [↩]
4. Philip R, Patidar P, Saran S, Agarwal P, Gupta K. Endocrine manifestations of celiac disease. Indian J Endocrinol Metab. 2012 December; 16(Suppl 2): S506–S508. [↩]
5. Pazianas M, Butcher GP, Subhani JM, et al. Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake. Osteoporosis International. Jan 2005;16(1):56-63. [↩]
6. Pazianas M, Butcher GP, Subhani JM, et al. Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake. Osteoporosis International. Jan 2005;16(1):56-63. [↩] [↩]
7. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
8. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
9. Philip R, Patidar P, Saran S, Agarwal P, Gupta K. Endocrine manifestations of celiac disease. Indian J Endocrinol Metab. 2012 December; 16(Suppl 2): S506–S508. [↩]
10. Zanchi C, Di Leo G, Ronfani L, Martelossi S, Not T, Ventura A. Bone metabolism in celiac disease. J Pediatr. 2008 Aug;153(2):262-5. doi: 10.1016/j.jpeds.2008.03.003 [↩]
11. Basha B, Rao DS, Han ZH, Parfitt AM. Osteomalacia due to vitamin D depletion: a neglected consequence of intestinal malabsorption. Am J Med. 2000 Mar;108(4):296-300. [↩]
12. Schmidt K, Powari M, Shirazi T, Vaidya B. Carpopedal spasm in an elderly man: an unusual presentation of coeliac disease. J R Soc Med. 2007 Nov;100(11):524-5. [↩]
13. Byrne MF, Razak AR, Leader MB, Sheehan KM, Patchett SE. Disabling osteomalacic myopathy as the only presenting feature of coeliac disease. Eur J Gastroenterol Hepatol. 2002 Nov;14(11):1271-4. [↩]