Celiac disease, menopause and bone-what are we missing?
Osteoporosis predominately affects post-menopausal women. However, celiac disease (CD), a systemic inflammatory condition resulting from an autoimmune reaction to dietary gluten, is a recognised cause of secondary osteoporosis. The study by Stuckey et al.,  aimed to compare the osteoporosis fracture prevalence and management (investigations and medication use) in individuals with self-reported celiac disease (recruited via CD support group) and individuals without CD (recruited via an endocrinology clinic and bone densitometry provider). Participants completed a survey regarding CD diagnosis/ symptomatology (if applicable), bone density assessment, fracture history, use of bone-preserving medication and any side-effects. Of the 131 participants with CD, 87% were diagnosed in adulthood (33% after age 50 years). Only 60% reported attributable symptoms at diagnosis; fatigue was the commonest symptom (82%) with variable gastrointestinal symptoms reported by approximately 70%. A diagnosis of osteoporosis predated the CD diagnosis in 21%. CD participants were significantly younger than non-CD (n=102) with mean age 50.7 versus 59.1 years (p<0.001) and females predominated (87% and 90% respectively). Overall, 34% of participants with CD reported a fragility fracture, predominately affecting the upper limb, and occurred before 50 years in 44%. Fracture prevalence in the non-CD group was greater (52% ; p=0.01%) with 50% occurring at age<50 years. Bone density scan was performed in ≥80% participants in both groups, although the results differed between the two groups. Low bone density or osteoporosis (defined according to T-score) was present in 28% and 30% respectively of CD participants and 62% and 23% of non-CD participants. Medication use differed between the two groups with 44% of CD and 82% of non-CD participants prescribed medications for low bone density or osteoporosis. Adjusting for age, calcium, vitamin D, menopausal hormone therapy (MHT), oral bisphosphonate and denosumab use were reported by more non-CD participants. More non-CD participants had ceased transdermal MHT; however, no difference was observed between groups in the proportion of participants reporting side effects or cessation of other medications. In the discussion, the authors review the literature regarding CD and osteoporosis. A gluten free diet is recommended as initial therapy for low bone density with adequate calcium intake and vitamin D supplements. Where osteoporosis is present, specific bone preserving therapy may be instituted; however, there is limited evidence to guide therapy.
This study addressed the issue of bone health in CD, a known cause of secondary osteoporosis. The prevalence of CD is reported as 1% with increasing incidence . Although children classically present with gastrointestinal symptoms, this study is consistent with previously published data indicating that adulthood is the peak time of diagnosis and symptoms may be non-specific . Calcium and vitamin D malabsorption leading to secondary hyperparathyroidism, osteomalacia, immune stimulation of osteoclastogenesis, low body mass index, malnutrition and hypogonadism contribute to bone loss in CD . CD is associated with other autoimmune diseases which may negatively impact bone health eg Type 1 diabetes mellitus. In the current study , participants with a self-reported diagnosis of celiac disease were compared to a non-CD group of predominately post-menopausal women recruited from an endocrine clinic or bone densitometry service, reflected in the higher fracture prevalence and medication use profile in the non-CD group. However, approximately one third of CD participants reported a fragility fracture or T-score defined osteoporosis, with a significant proportion aged <50 years). This is consistent with previous studies and meta-analysis reporting a 25-43% increased risk of fracture in untreated CD patients compared with controls [3,5,6] with a predominance of radius fractures . Osteopenia and osteoporosis (defined according to T scores) is common, ranging from 38-72% at diagnosis [3,5,6]. At diagnosis, assessment of serum parathyroid hormone (PTH), 25 OH vitamin D, calcium, albumin and alkaline phosphatase levels and celiac antibody titres is recommended . Higher PTH, anti-tissue transglutaminase and endomysial antibody titres correlate with lower BMD and fracture . Bone densitometry is recommended at diagnosis2 or after one year of a gluten free diet ..
As advocated by the authors  and guidelines [2-4], a gluten free diet promotes intestinal healing, reduces systemic inflammation and is associated with improvements in BMD and reduced fracture rates [3,7]. No data regarding compliance with a gluten free diet was provided in this study. Although a small sample size, it is reassuring that the use of calcium supplements or oral bisphosphonates was not associated with reports of increased gastrointestinal side effects in the CD compared to non-CD group. However, the authors do not provide any data regarding efficacy of these medications in either group and indeed a systematic review found no evidence to support anti-resorptive therapy use in addition to diet [3,7].
In answer to the question “what are we missing?”. This study by Stuckey and co-authors highlights the potential non-specific presentation of CD and the prevalence of osteoporosis in persons with CD indicating the need for osteoporosis risk assessment [2,3,6]. This study also provides evidence in support of screening for CD in individuals presenting with osteoporosis or in the setting of persistent bone loss despite MHT . This paper emphasizes the importance of a gluten free diet for bone health in CD and underscores the lack of data regarding efficacy of other therapeutic options including MHT.
Amanda Vincent, MBBS, B Med Sci, PhD, FRACP
Department of Endocrinology, Monash Health, Clayton 3168, Victoria, Australia
IMS Board member
1. Stuckey BGA, Mahoney LA, Dragovic S, Brown SJ. Celiac disease and bone health: is there a gap in the management of postmenopausal osteoporosis? Climacteric 2020: 1-7.
4. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA, American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013 May;108(5) 656-76.