Osteoporosis

Woman with long standing osteoporosis. Courtesy of Wikimedia.

What Is Osteoporosis?

Osteoporosis is a metabolic bone disorder characterized by diminished bone mass (density) with normal cell appearance but fragile bone strength that prediposes to broken bones, and with high bone turnover.

This condition usually goes undetected until late when loss of height or a bone fracture occurs. In fact, each year  1.5 million fractures mainly of the hip, spine and wrist are attributed to osteoporosis. Compression fractures of vertebrae bones are the most common, accounting for 700,000 cases.

Bone is composed of specialized connective tissue called osseous tissue. Osseous tissue is made up of living bone cells (osteocytes) that are embedded in a hard matrix (framework) of calcified substance.

Bone matrix contains collagen fibers and the minerals calcium phosphate and calcium carbonate, which provide strength to bone. The copper enzyme, lysyl oxidase, is involved in the cross-linking of collagen in forming the framework for depositing calcium and other minerals to build and repair bone.

Q: How do osteocytes function in bone?

A: Osteocytes maintain the health of bone by their metabolic activity in regulating normal bone turnover. Bone turnover is the breaking down and removal of old or damaged bone and rebuilding or remodeling of healthy bone that is ongoing throughout life. The bone formation process takes about 3 months to complete.

Osteoporosis develops from failure of the body to maintain health and to provide bone tissue with adequate nutrition for proper function. Risk factors that can be modified include: low calcium intake, sedentary lifestyle, smoking, drinking alcohol excessively, eating a diet with excessive caffeine, protein, and phosphate, and taking certain medications over a long time such as steroids, thyroid preparations, the anti-convulsive drug phenytoin, aspirin, antacids, anticoagulants, some diuretics, and some chemotherapeutic drugs. See below for a fuller description.

In addition to celiac disease, osteoporosis is associated with advancing age, family history, nulliparity (no pregnancies) and post-menopause in females, certain disorders such as hyperthyroidism, hypogonadism, inflammatory bowel disease like Crohn’s disease, multiple myeloma, anorexia nervosa, and Cushing’s disease.

Bone strength is easily measured by testing bone mineral density (BMD). BMD is evaluated by DEXA scan (dual-energy X-ray absorptiometry).  DEXA at the femoral neck and lumbar spine is considered the gold standard to confirm the diagnosis of osteoporosis.  Results are expressed as T and Z scores. T scores compare the result with a 20 to 40 year old helathy person while  Z scores compare the result with persons in the same age group. Both are measured in standard deviations (SD).

According to WHO criteria (World Health Organization), a T-score of -1 SD or greater denotes normal bone, a T-score between −1 to −2.5 SD denotes osteopenia, and a T-score of −2.5 or more denotes osteoporosis.1

Treatment is aimed to preserve and increase bone density, minimize symptoms for better quality of life and reduce risk of bone fractures.

What Is Osteoporosis In Celiac Disease and/or Gluten Sensitivity?

The cumulative effects of gluten-induced inflammation, treatment delay, and malabsorption result in lower bone density and bone fragility.2

• Relationship between osteopenia/osteoporosis and celiac disease. Osteoporosis is a complication of celiac disease and is a frequent atypical presentation of celiac disease, especially in adults. Atypical or silent celiac disease may go undiagnosed for many years due to confusing symptoms, or no symptoms, and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis.1
• Relationship between osteopenia/osteoporosis and intestinal damage. Patients with partial villous atrophy presented with similar bone loss characteristics as did patients with severe villous atrophy meaning the severity of osteopenia/osteoporosis does not depend on the severity of intestinal damage.3
• Relationship between osteopenia/osteoporosis and chronic inflammation. Chronic inflammation can affect bone and mineral metabolism because of alterations in both systemic and local regulatory factors.4
• Relationship between osteopenia/osteoporosis and bone mineral density. Reduced bone mineral density (BMD) is frequently found in individuals with untreated celiac disease, possibly due to calcium and vitamin D malabsorption, release of pro-inflammatory cytokines, and misbalanced bone remodeling. In a study of 54 patients at diagnosis of celiac disease, a statistically significant association was seen between BMD and age of onset, duration of illness, serum tTGA levels, serum vitamin D levels, and cellular changes seen on biopsy. BMD should be measured in all newly diagnosed celiac patients and calcium and vitamin D supplementation included in the treatment regimen.5
• Relationship between osteopenia/osteoporosis and bone strength. A case-control study investigating the microarchitecture and biomechanical properties of bone in celiac disease suggest a potential structural mechanism for skeletal fragility in celiac disease. Women with celiac disease had abnormal bone mineral density (BMD) and microarchitecture at both radius (wrist) and tibia (lower leg). Trabecular bone (inner portion of a bone) was preferentially affected. These deficits were associated with lower estimates of skeletal strength.6
• Relationship between osteopenia/osteoporosis and diet. A gluten-free diet promotes a rapid increase in bone mineral density that leads to complete recovery of bone mineralization in children. Children may attain normal peak bone mass if the diagnosis is made and treatment is given before puberty, thereby preventing osteoporosis in later life. However, a gluten-free diet improves, but rarely normalizes, bone mineral density in patients diagnosed with celiac disease in adulthood.7
• Relationship between H. pylori infection and osteoporosis. H. pylori infection is an associated disorder of celiac disease that can cause a significant decrease in mean lumbar bone mineral density (but not at the femoral neck and total femur). H. pylori infection causes chronic gastritis by inducing a localized and systematic inflammatory response that may increase the concentrations of tumor necrosis factor-α, interleukin-1, and interleukin-6, which are known to affect bone mineral density.8
• Relationship between osteopenia/osteoporosis and bisphosphonate drugs. Bisphosphonates such as zoledronic acid are a class of drugs that inhibit bone resorption. A small pilot study investigating 28 newly diagnosed celiac disease patients about 18 years of age with either gluten free diet and zoledronic acid, or a calcium and cholecalciferol (vitamin D) supplemented gluten free diet reported that there were no significant difference in effectiveness. Patients were enrolled and followed prospectively for one year. Replication of this study with a larger sample size that includes older adults may be more representative of the adult celiac disease population.9

How Prevalent Is Osteoporosis In Celiac Disease and/or Gluten Sensitivity?

Approximately 75% of newly diagnosed patients with celiac disease have low bone mineral density (BMD). And when matched by age and gender to a non-affected population, celiac patients have a 40% greater risk for bone fracture. Even with a silent or extra-intestinal presentation such as dermatitis herpetiformis or dementia, low bone mass is frequently found. One-third of newly diagnosed cases are over 60 years of age which coincides with a period of an increased risk of falls only worsened by the presence of co-morbidities.2

Bone mineral density findings of study patients at diagnosis of celiac disease showed the following pattern: 40% with osteopenia, 26% with osteoporosis, and 34% with normal bone mineral density.10

A study of bone mineral density according to WHO (World Health Organization) criteria at the time of diagnosis, found these results: a normal DEXA scan at lumbar spine was observed in 71 patients (42%; T-score mean value −0.1 plus or minus 0.7), whilst 62 were osteopenic (37%; T-score mean value −1.7 plus or minus 0.4) and 36 osteoporotic (21%; T-score mean value −3.1 plus or minus 0.4). A normal DEXA at femoral neck was observed in 72 patients (43%; mean value −0.3 plus or minus 0.6), whilst 75 were osteopenic (44%; mean value −1.7 plus or minus 0.4) and 22 osteoporotic (13%; mean value −3.1 plus or minus 0.4).1

What Are The Symptoms Of Osteoporosis?

There are no symptoms in the early stages of osteoporosis. At the other end, up to 20% of patients undergoing hip surgery die due to complications and 50% will be unable to walk without assistance.

• Osteoporosis is marked by progressive skeletal changes, especially in loss of height which can be as much as 6 inches, and form of the spine, with eventual disability from pain and loss of mobility.
• The spine can develop into a stooped posture with kyphosis (also called a “dowager’s hump”) or the back may appear straight while the spine develops an S shape from side to side.
• Pain almost anywhere in the spine can be caused by fractures of the bones of the spine (compression fractures) that occur without an injury. The pain may occur suddenly or slowly over time.
• Women with celiac disease have a much higher rate of fractures during the 10 year period prior to diagnosis and 5 years afterward.2

How Does Osteoporosis Develop In Celiac Disease and/or Gluten Sensitivity?

• Osteoporosis in celiac disease results from chronic inflammation causing villous atrophy and malabsorption of nutrients.11 Malabsorption causes deficiency of calcium primarily, vitamin D in particular which is needed for calcium absorption, and other micronutrients including magnesium, vitamin K, zinc, iron, manganese, copper, and boron.
• Bone weakening might result from these mechanisms:

1. Metabolic disturbances of bone remodeling affecting trabecular and cortical bone masses and the mechanical quality of the bone material, and
2. A reduction of muscle strength which impairs bone architectural design and mass of cortical bone.12

• Diet that does not contain the necessary nutrients for bone health.
• Physical inactivity that commonly results in celiac disease from nutritional deficiencies and disorders such as anemia.
• In males, elevated prolactin hormone and follicle stimulating hormone (FSH), which are associated disorders in celiac disease, indicate an imbalance of hypothalmus-pituitary level, increasing their risk of developing osteoporosis.
  

  Illustration by Patricia Grace-Farfaglia. Nutrients. 2015 May 7;7(5):3347-3369.

Does Osteoporosis Respond To Gluten-Free Diet?

Yes. The most effective treatment for celiac disease and related co-morbidities (diseases), the gluten-free diet, is without dispute in the literature. Yet, improvements in bone mineral density (BMD) after treatment can take up to five years after mucosal recovery.2

Gluten free diet significantly improves bone mineral density, bone metabolism and nutrition even in post-menopausal women and in patients with incomplete mucosal recovery.10,13,14

• A gluten-free diet promotes a rapid increase in bone mineral density that leads to complete recovery of bone mineralization in children. Children may attain normal peak bone mass if the diagnosis is made and treatment is given before puberty, thereby preventing osteoporosis in later life.15

• A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value by DEXA scan in 175 consecutive celiac patients at time of diagnosis.1

• Parathyroid hormone levels improve over time following treatment suggesting continuing long-term benefit of gluten withdrawal on bone metabolism.16

• Response to gluten free diet is similar for patients with partial villous atrophy and severe villous atrophy.17

Treatment failure may actually be the result of a highly processed gluten free diet as it is associated with small bowel bacterial overgrowth (SIBO). A highly processed gluten free diet (snacks such as cookies, crackers, pretzels) has been shown to alter the gut microbiome and increase gastrointestinal symptoms which leads to an increased permeability of the epithelial barrier (leaky gut) in patients with celiac disease. The health of the gut microbiota and the symptoms related to SIBO impact normalization of bone metabolism.2

Another Caution: just as adequate calcium (1200 mg to 1500 mg a day) is primarily required for bone health, EXCESSIVE fiber, protein, and sodium in the diet harm bone health by decreasing calcium absorption and the body’s ability to use calcium.

6 Steps To Improve Osteoporosis In Celiac Disease and/or Gluten Sensitivity:

• 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 Osteoporosis In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Abnormal Skeletal Strength and Microarchitecture in Women with Celiac Disease.” This case-control study investigating the microarchitecture and biomechanical properties of bone in celiac disease (CD) suggest a potential structural mechanism for skeletal fragility in CD and support further research into the pathogenesis of fracture in this population.

In a university hospital out-patient facility 33 premenopausal women with newly diagnosed CD and 33 healthy controls were evaluated for bone mineral density. Areal BMD (aBMD) by DXA scan. Trabecular and cortical volumetric BMD (vBMD) and microarchitecture by high resolution peripheral computed tomography (HR-pQCT) of the distal radius and tibia. Whole bone stiffness estimated by finite element analysis. Parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD) and bone turnover markers.

Groups had similar age, race and BMI. Both groups had sufficient 25OHD (vitamin D), and normal calcium and PTH (parathyroid hormone). Areal BMD was lower in CD. By HR-pQCT, CD had lower trabecular vBMD, fewer, more widely and irregularly spaced trabeculae at both radius and tibia (8-33%). At the tibia, they also had lower total density (8%) and thinner cortices (10%). Whole bone stiffness and failure load were lower (11-21%) in CD at both sites. Biomechanical deficits were associated with trabecular abnormalities.

Conclusion: Women with CD had abnormal vBMD and microarchitecture at both radius and tibia. Trabecular bone was preferentially affected. These deficits were associated with lower estimates of skeletal strength.6

“Bones of Contention: Bone Mineral Density Recovery in Celiac Disease-A Systematic Review.” This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist.

Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied.2

“Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet.” This study investigating the prevalence of osteopenia/osteoporosis in patients with new diagnosis of celiac disease and to assess the impact of gluten free diet on bone mineral density (BMD) 1 year after the diagnosis by dual-energy X-ray absorptiometry (DEXA scan) to determine the population appropriate for this test showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value.

Included in this study were 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value less than -1 at diagnosis.

According to WHO criteria, at the time of diagnosis, a normal DEXA at lumbar spine was observed in 71 patients (42%; T-score mean value −0.1 ± 0.7), whilst 62 were osteopenic (37%; T-score mean value −1.7 ± 0.4) and 36 osteoporotic (21%; T-score mean value −3.1 ± 0.4) with a total population mean T-score value of −1.3 ± 1.3. A normal DXA at femoral neck was observed in 72 patients (43%; mean value −0.3 ± 0.6), whilst 75 were osteopenic (44%; mean value −1.7 ± 0.4) and 22 osteoporotic (13%; mean value −3.1 ± 0.4) with a total population mean T-score value of −1.3 ± 1.1.

Researchers state, “We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged more than 30 years, taking into account each risk factor in single patients.”20

“Effect of zoledronic acid on bone mineral density in patients of celiac disease: a prospective, randomized, pilot study.” This initial study investigating the effect of zoledronic acid on bone mineral density (BMD) in young patients with celiac disease found that administration of zoledronic acid was not better than gluten free diet alone in increasing BMD in celiac disease patients with low BMD.

A total of 28 patients newly diagnosed with celiac disease were randomized to receive gluten free diet with calcium and cholecalciferol (group A), and zoledronic acid (group B). Excluded were postmenopausal women, pregnant women, patients taking drugs (currently or within last one year viz. steroids, anticonvulsants, anticoagulants, calcium supplements) and having diseases (chronic liver disease, chronic kidney disease, thyrotoxicosis, other malabsorptive disorders) known to affect BMD, smokers and persons consuming alcohol (3 drinks/day or more).

Baseline biochemical tests and T-score by dual energy x-ray absorptiometer were done and repeated after 12 months.

The T-score showed improvement in the control arm (group A) from -3.31 ± 1.46 to -2.12 ± 1.44, a gain of 35.9 per cent and in drug arm (group B) -2.82 ± 1.27 to -1.06 ± 1.84, registering a gain of 62.4 per cent. However, there was no difference in improvement of T-score in zoledronic acid group as compared to the control group.9

“Prevalence and predictors of abnormal bone mineral metabolism in recently diagnosed adult celiac patients.” This study investigating the prevalence of low bone mineral density (BMD) in recently diagnosed adult celiac patients and aiming to identify the factors associated with this found that low BMD is common in newly diagnosed adult celiac patients with approximately one fifth of them having osteoporosis and low vitamin D level.

BMD was measured in 54 newly diagnosed adult celiac patients between February 2008 and April 2009 and its correlation with clinical and biochemical parameters was analyzed. Fifty-four (24 male) newly diagnosed celiac patients ages 18-50 were included. Thirty-nine (72.2 %) presented with intestinal symptoms and the rest with extraintestinal symptoms. Low vitamin D levels were seen in 11 (20.3 %) patients and elevated iPTH (secondary hyperparathyroidism) in 12 (22.2 %) patients. Twenty-one (39 %) patients had normal BMD, 23 (43 %) had osteopenia (T-score -1 to -2.5), and 10 (18 %) patients had osteoporosis (T-score <-2.5). A statistically significant association was seen between BMD and age of onset, duration of illness, serum tTGA levels, serum vitamin D levels, and cellular changes seen on biopsy. BMD should be measured in all newly diagnosed celiac patients and calcium and vitamin D supplementation included in the treatment regimen.21

“Adult celiac disease with severe or partial villous atrophy: a comparative study.” This retrospective study investigating the impact of partial villous atrophy on the clinical presentation of adult celiac disease (ACD) versus patients with severe villous atrophy found partial villous atrophy in 21% of patients with ACD. Patients with partial villous atrophy presented with similar clinical, biological and immune characteristics and outcomes as did patients with severe villous atrophy. Diarrhea, malabsorption syndrome and osteopenia were independent of the degree of villous atrophy meaning the extent of these conditions does not depend on the severity of intestinal damage.

Medical files of 48 patients with ACD diagnosed between 1992 and 2003 were retrospectively studied. The diagnosis was based on the presence of intestinal villous atrophy, with increases in intraepithelial lymphocytes and circulating celiac specific antibodies. Villous atrophy was classified as severe (subtotal and total) or partial. Symptoms, biological signs of malabsorption, immune markers, bone mineral density at diagnosis and response to gluten-free diet were recorded.

At diagnosis, ten patients (four M/six F) had partial villous atrophy and 38 patients (five M/33 F) had severe villous atrophy, with a median age of 54 and 33 years, respectively. Positivity for specific antibodies, HLA typing and frequency of autoimmune disease at diagnosis were similar in both groups, as was their response to gluten-free diet.22

“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) over 4 years treatment with a gluten free diet demonstrated that increased calcium intake could potentially compensate for the reduced fractional calcium absorption in treated adult celiac disease patients, but may not normalize the BMD. Inverse correlation between parathyroid hormone (PTH) and time following treatment suggests continuing long-term benefit of gluten withdrawal on bone metabolism.16

“Increased prevalence of celiac disease and need for routine screening among patients with osteoporosis.” This study evaluating 266 patients with and 574 without osteoporosis demonstrated the prevalence of celiac disease in osteoporosis is high enough to justify a recommendation for serologic screening of all patients with osteoporosis for celiac disease.23

“Analysis of the structure and strength of bones in celiac disease patients.” This study investigating pathogenesis of bone loss and weakening in celiac disease patients demonstrated that bone weakening might result from 1) metabolic disturbances of bone remodeling affecting trabecular and cortical bone masses and the mechanical quality of the bone material, and 2) a reduction of muscle strength impairing the modeling dependent optimization of bone architectural design and mass of cortical bone. Gluten free diet seems to correct almost exclusively the metabolically induced disturbances.24

“The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult celiac disease patients.” This study evaluating the impact of a 1-year gluten free diet on bone metabolism and nutritional status in newly diagnosed celiac disease patients demonstrated that celiac disease patients are at high risk for developing a low bone mineral density (BMD) and bone turnover impairment. A one year gluten free diet improved this situation in the 57% which showed mucosal recovery of the small intestine. Between postmenopausal and fertile women there were significant differences in BMD and several bone markers.25

CASE REPORT SUMMARIES

“Causes of osteoporosis: don’t forget celiac disease.” This case report describes a 60 year old woman presenting with refractory osteoporosis (would not respond to treatment). Osteoporosis was confirmed, osteomalacia was ruled out based on transiliac bone biopsy, and celiac disease was revealed. Blood levels of calcium and phosphorus were normal; vitamin D, folic acid, and vitamin B12 were low; AGA (anti-gliadin) and EMA (endomysial) antibodies were significantly elevated. Careful diagnostic evaluation of osteoporosis is necessary due to consequences of missed diagnosis.26

1. Pantaleoni S, Luchino M, Adriani A, Pellicano R, Stradella D, Ribaldone DG, Sapone N, Isaia GC, Di Stefano M, Astegiano M. Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet. ScientificWorldJournal. 2014;2014:173082. doi: 10.1155/2014/173082. [↩] [↩] [↩] [↩]
2. Grace-Farfaglia P. Bones of Contention: Bone Mineral Density Recovery in Celiac Disease-A Systematic Review. Nutrients. 2015 May 7;7(5):3347-3369. [↩] [↩] [↩] [↩] [↩] [↩]
3. Malamut G, Matysiak-Budnik T, Grosdider E, Jais JP, Morales E, Damotte D, Caillat-Zucman S, Brousse N, Cerf-Bensussan N, Jian R, Cellier C. Adult celiac disease with severe or partial villous atrophy: a comparative study. Gastroenterol Clin Biol. 2008 Mar;32(3):236-42. doi: 10.1016/j.gcb.2008.02.011. [↩]
4. Bianchi ML, Bardella MT. Bone in celiac disease. Osteoporos Int. 2008 Dec;19(12):1705-16. doi: 10.1007/s00198-008-0624-0. [↩]
5. Chakravarthi SD, Jain K, Kochhar R, Bhadada SK, Khandelwal N, Bhansali A, Dutta U, Nain CK, Singh K. Prevalence and predictors of abnormal bone mineral metabolism in recently diagnosed adult celiac patients. Indian J Gastroenterol. 2012 Jul;31(4):165-70. [↩]
6. Stein EM, Rogers H, Leib A, McMahon DJ, Young P, Nishiyama K, Guo XE, Lewis S, Green P, Shane E. Abnormal Skeletal Strength and Microarchitecture in Women with Celiac Disease. J Clin Endocrinol Metab. 2015 Apr 13:jc20151392. [↩] [↩]
7. Capriles VD, Martini LA, Arêas JA. Metabolic osteopathy in celiac disease: importance of a gluten-free diet. Nutr Rev. 2009 Oct;67(10):599-606. doi: 10.1111/j.1753-4887.2009.00232.x. [↩]
8. Chung YH, Gwak JS, Hong SW, Hyeon JH, Lee CM, Oh SW, Kwon H. Helicobacter pylori: A Possible Risk Factor for Bone Health. Korean J Fam Med. 2015 Sep;36(5):239-44. doi: 10.4082/kjfm.2015.36.5.239. Epub 2015 Sep 18. [↩]
9. Kumar M, Rastogi A, Bhadada SK, Bhansali A, Vaiphei K, Kochhar R. Effect of zoledronic acid on bone mineral density in patients of celiac disease: a prospective, randomized, pilot study. Indian J Med Res. 2013 Dec;138(6):882-7. [↩] [↩]
10. Sategna-Guidetti C, Grosso SB, Grosso S, et al. The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients. Alimentary Pharmacology and Therapeutics. Jan 2000;14(1):35-43. [↩] [↩]
11. Bianchi ML, Bardella MT. Bone in celiac disease. Osteoporos Int. 2008 Dec;19(12):1705-16. doi: 10.1007/s00198-008-0624-0. Epub 2008 Apr 17. [↩]
12. Ferretti J, Mazure R, Tanoue P, et al. Analysis of the structure and strength of bones in celiac disease patients. American Journal of Gastroenterology. Feb 2003;98(2):382-90. [↩]
13. 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. [↩]
14. Ferretti J, Mazure R, Tanoue P, et al. Analysis of the structure and strength of bones in celiac disease patients. American Journal of Gastroenterology. Feb 2003;98(2):382-90. [↩]
15. Capriles VD, Martini LA, Arêas JA. Metabolic osteopathy in celiac disease: importance of a gluten-free diet. Nutr Rev. 2009 Oct;67(10):599-606. doi: 10.1111/j.1753-4887.2009.00232.x. [↩]
16. 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. [↩] [↩]
17. Malamut G, Matysiak-Budnik T, Grosdider E, Jais JP, Morales E, Damotte D, Caillat-Zucman S, Brousse N, Cerf-Bensussan N, Jian R, Cellier C. Adult celiac disease with severe or partial villous atrophy: a comparative study. Gastroenterol Clin Biol. 2008 Mar;32(3):236-42. doi: 10.1016/j.gcb.2008.02.011. [↩]
18. 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. [↩]
19. 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. [↩] [↩] [↩] [↩] [↩] [↩] [↩]
20. Pantaleoni S, Luchino M, Adriani A, Pellicano R, Stradella D, Ribaldone DG, Sapone N, Isaia GC, Di Stefano M, Astegiano M. Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet. ScientificWorldJournal. 2014;2014:173082. doi: 10.1155/2014/173082. [↩]
21. Chakravarthi SD, Jain K, Kochhar R, Bhadada SK, Khandelwal N, Bhansali A, Dutta U, Nain CK, Singh K. Prevalence and predictors of abnormal bone mineral metabolism in recently diagnosed adult celiac patients. Indian J Gastroenterol. 2012 Jul;31(4):165-70.. [↩]
22. Malamut G, Matysiak-Budnik T, Grosdider E, Jais JP, Morales E, Damotte D, Caillat-Zucman S, Brousse N, Cerf-Bensussan N, Jian R, Cellier C. Adult celiac disease with severe or partial villous atrophy: a comparative study. Gastroenterol Clin Biol. 2008 Mar;32(3):236-42. doi: 10.1016/j.gcb.2008.02.011. [↩]
23. Stenson WF, Newberry R, Lorenz R, Baldus C, Civitelli R. Increased prevalence of celiac disease and need for routine screening among patients with osteoporosis. Archives of Internal Medicine. Feb 28, 2005;165(4):393-9. [↩]
24. Ferretti J, Mazure R, Tanoue P, et al. Analysis of the structure and strength of bones in celiac disease patients. American Journal of Gastroenterology. Feb 2003;98(2):382-90. [↩]
25. Sategna-Guidetti C, Grosso SB, Grosso S, et al. The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients. Alimentary Pharmacology and Therapeutics. Jan 2000;14(1):35-43. [↩]
26. Scharla S. Causes of osteoporosis: don’t forget celiac disease.Deutsche Medizinische Wochenschrift. Apr 25, 2003;128(17):916-9. [↩]