Bone Disease in Chronic Pancreatitis: A Complex Phenomenon
Condition: Chronic Pancreatitis; Osteopenia; Osteoporosis
MeSH terms: Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Pancreatitis; Pancreatitis, Chronic
Study type: Observational

Summary: 
      The purpose of this study is to define the prevalence of low bone density
      (osteopenia/osteoporosis) in patients with chronic pancreatitis. Secondary aims include
      investigating the prevalence of hypogonadism (low sex hormones) in patients with chronic
      pancreatitis and determining if hypogonadism and/or use of narcotic pain medications are risk
      factors for low bone density in this patient population.

        1. Hypothesis:

           Patients with chronic pancreatitis are at increased risk of low bone density
           (osteopenia/osteoporosis), and hypogonadism (low sex hormone levels) and narcotic pain
           medication use are independent risk factors for the development of low bone density in
           this patient population.

        2. The outcome measures include:

           i) Prevalence of low bone density (osteopenia/osteoporosis) in patients with chronic
           pancreatitis (as determined by DXA scan and fracture history).

           ii) Prevalence of hypogonadism (low sex hormones) in patients with chronic pancreatitis
           (as determined by sex hormone levels and clinical history).

           iii) Identification of hypogonadism and/or opioid use as risk factors for low bone
           density in patients with chronic pancreatitis (as determined by univariate and
           multivariate analysis of multiple risk factors).

        3. After obtaining written consent from potential subjects, a questionnaire will be
           performed outlining risk factors for low bone density. Dual X-ray absorptiometry (DXA
           scan) will be performed to evaluate for low bone density and a blood test will be
           performed to evaluate for low sex hormones, low levels of vitamin D, and other risk
           factors for low bone density.
    

Detailed description: 
      Chronic pancreatitis is defined as a continuing inflammatory disease of the pancreas
      characterized by irreversible morphologic changes that typically cause pain and/or permanent
      loss of function. The annual incidence of chronic pancreatitis in the Unites States is 5-12
      per 100,000 and prevalence of 50 per 100,000 persons though the incidence is rising over time
      . The most common symptoms related to chronic pancreatitis include steatorrhea and abdominal
      pain. Pain with chronic pancreatitis can be severe and debilitating and opioid pain
      medications are frequently utilized in the management of these symptoms .

      A number of chronic malabsorptive disorders, including Crohn's disease, celiac disease, and
      cystic fibrosis are known to be associated with decreased bone mineral density. Similarly,
      there is increasing data supporting low bone mineral density (osteopenia and osteoporosis) in
      patients with chronic pancreatitis, though the exact mechanisms remain unclear.

      A meta-analysis of 11 observational studies of chronic pancreatitis reported the prevalence
      of osteopenia to be 39.8% and osteoporosis 23.4%, with the cumulative prevalence of low bone
      density (osteopenia and osteoporosis) being almost 65%. Interestingly, out of the eleven
      studies in this meta-analysis, eight were performed in Europe, two in India, and one in South
      America.

      Some studies in chronic pancreatitis have described a link between Vitamin D deficiency and
      risk for low bone density. Other proposed risk factors for low bone density in this patient
      population include age, gender, malnutrition, alcohol use, smoking, and variation and
      duration of pancreatitis. However, other potential novel risk factors for low bone density
      exist in patients with chronic pancreatitis. These factors include chronic use of opioid
      medications and hypogonadism.

      Opioid use is prominent in patients with chronic pancreatitis. At least 85% of patients
      suffering from chronic pancreatitis will develop pain and despite many different treatment
      methods, many patients with chronic pancreatitis do not get respite from their pain, even
      after several years. Therefore, up to 50% or more of all patients with chronic pancreatitis
      will utilize opioid medications as part of their pain management strategy. Opioid medication
      use has been shown to be a risk factor for low bone density. The exact mechanism behind
      opioid-induced low bone density is not known but is likely multi-factorial.

      To date, the prevalence of hypogonadism in patients with chronic pancreatitis is unknown but
      would be expected to be higher than the general population due to the risk factors of opioid
      use, chronic illness, and potentially malnutrition. This warrants further investigation as a
      higher prevalence of hypogonadism could directly impact bone health in this cohort, not to
      mention potential effects of hypogonadism on quality of life and fertility.

      This research project will utilize Dual X-ray absorptiometry (DXA scan) and clinical history
      to determine the prevalence of low bone density (osteopenia/osteoporosis) in our cohort;
      blood draw, clinical history, and questionnaire to determine prevalence of hypogonadism in
      our cohort; and blood draw, clinical history, and questionnaire to examine specific risk
      factors for low bone density in our cohort.

      After obtaining written consent from potential subjects, a questionnaire will be performed
      outlining smoking history, alcohol use history, fracture history, signs/symptoms of
      hypogonadism, exercise patterns, and opioid medication use history. A one-time Dual X-ray
      absorptiometry (DXA scan) will be performed on each subject. A one-time blood draw will be
      performed on each subject, with the following lab tests being performed on each subject:

        -  25-hydroxy Vitamin D

        -  Comprehensive Metabolic Panel

        -  Total Testosterone (males)

        -  Estradiol (females)

        -  Lutenizing hormone (LH)

        -  Follicle-stimulating hormone (FSH)

        -  Steroid hormone binding globulin (SHBG)

        -  Prolactin
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Both males and females with diagnosis of chronic pancreatitis
      
Keywords: Chronic Pancreatitis; Osteopenia; Osteoporosis; Hypogonadism; Opioid medications