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Bone Alkaline Phosphatase (BALP), Elevated

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Vertebrae. Courtesy FreePik.com

Vertebrae. Courtesy FreePik.com

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 dietIn 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:

Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both calcium and gut health.

  • Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
  • A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
  • Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

  • Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
  • Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.7
  • The intestinal lining may take up to a year to heal.
  • 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).

Here Are Major Inflammatory Food Types That Reduce Healing:

  • Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.8
  • Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
  • Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.8
  • Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.8.
  • Excessive Refined White Flours (bran layer removed)Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.8
  • Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
  • Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.8
  • Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.8

Here Are Important Anti-Inflammatory Food Types to Promote Health:

  • Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
  • Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes lettuce, kale, onion, broccoli, garlic, and others.
  • High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
  • Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
  • Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
  • Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
  • Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
  • Protective Herbs and Spices.  See below #6 below for examples.
  • 3 Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

  • 4 Manage Your Medications Safely:

Certain prescription drugs deplete calcium that causes elevated BALP. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

 This is not a complete listing.

ANTACIDS / ULCER MEDICATIONS

  • Pepcid®, Tagamet®, Zantac® deplete Calcium.
  • Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®) deplete Calcium.

ANTIBIOTICS disrupt intestinal permeability.

ANTI-INFLAMMATORIES disrupt intestinal permeability.

  • Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Calcium.
  • Aspirin and Salicylates deplete Calcium.

ANTICONVULSANTS

  • Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon® deplete Calcium.

ANTIVIRAL AGENTS

DIURETICS

  • Potassium Sparing Diuretics (Midamor®, Aldactone®, Dyrenium® and others) deplete Calcium.
  • 5Nutritional Supplements To Help Correct Deficiencies:

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

  • Multivitamin/mineral combination once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.
  • Calcium citrate is the best absorbed of calcium supplements. Calcium carbonate is a poor choice.
  • Vitamin D3 for better absorption of calcium as prescribed following blood test for status.

Storage NoteStore container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.

  • 6Manage Natural Remedies: 

Hydration:

  • Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
  • If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
  • Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
  • What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.

Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

  • Raspberry.
  • Carrot is also a cleansing digestive tonic.
  • Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
  • Redbeets also stimulate and improve digestion and are easily digested.
  • Cabbage also stimulates and improves digestion and is also a liver decongestant.
  • Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
  • Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

  • Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
  • Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
  • Parsley also relieves indigestion.
  • Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion.
  • Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

  • Cloves are also antispasmodic.
  • Nutmeg is also useful for indigestion.
  • Ginger.

Exercise Helps:

Exercise improves circulation and rids the body of toxins.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal.

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. []

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