Osteoporosis and Gastrointestinal Disease
Lactose intolerance can make it difficult to get enough calcium and vitamin D to maintain healthy bones. Get tips on protecting your bones if you. Most of my life I've suffered from Irritable Bowel Syndrome (IBS). Since the osteoporosis diagnosis, I looked in deeper for any connection. The risk of secondary osteoporosis is heightened in patients diagnosed with celiac disease (CD), inflammatory bowel disease (IBD), irritable bowel syndrome, .Irritable bowel syndrome (IBS) - causes, symptoms, risk factors, treatment, pathology
In an animal model, ibandronate Boniva, Roche was shown to have a potential benefit on the gut disease itself, decreasing the potential for carcinogenesis in a murine model of ulcerative colitis. Esophageal ulcerations have been reported with prolonged contact, particularly if dysmotility exists. Twenty-three cases of esophageal cancer were identified between and by the FDA Office of Surveillance and Epidemiology.
Thirty-one cases have been reported in Europe and Japan using alendronate, and 10 other cases had suspected associations with risedronate, ibandronate, and etidronate. These carcinomas occurred with Barrett esophagus.
The median duration of exposure was 2. The incidence is much lower with repeated doses.
This reaction is most common during the first week and can last for 3—5 days with lymphopenia, which will resolve. Hypocalcemia can occur if the patient has pretreatment calcium or vitamin D deficiency, or renal insufficiency with secondary hyperparathyroidism.
Hypocalcemia should be managed with 1, mg calcium and —1, IU vitamin D daily before bisphosphonates. Rapid infusions of IV pamidronate or zoledronate can alter renal function and cause rare cases of renal failure.
This risk is reduced by slowing the infusion rate and ensuring that the patient is adequately hydrated. Monitoring of renal function is required. Osteonecrosis of the jaw is a nonhealing ulcer of the jaw with exposed bone that presents after 8 weeks in the absence of radiotherapy.
For example, in the zoledronate HORIZON trials, which randomized 10, patients to zoledronate or placebo annually for approximately 3 years, there were 2 cases of osteonecrosis, 1 on placebo and 1 on active drug. Suppression of bone turnover remains unproven and would not explain why the jaw is the only site presenting with this problem.
It is advised that patients undergo routine dental examinations including a discussion regarding the risks and benefits of bisphosphonates prior to initiation of therapy and that they are reassured that osteonecrosis is rare. An active prevention protocol should be initiated before dental procedures. Unusual subtrochanteric fractures of the femoral shaft have been reported but in small numbers in patients on long-term bisphosphonates.
There is a pain prodrome, and the fractures can occur in the absence of trauma. Contralateral pain with mirror-image abnormal findings detected on bone scans and magnetic resonance imaging has also been described. The mechanism of action is not known but may represent an inability to heal microfractures with accumulated damage in a highly stressed skeletal site.
The incidence of atrial fibrillation was 1. Ocular findings with bisphosphonates uveitis, pain episodes, and photophobia are rarely seen with either oral or IV bisphosphonates. This is an unpredictable and idiosyncratic reaction. Prolonged skeletal half-life of bisphosphonates per -mits a continued effect eg, 5 years after initial use.
Secondary Osteoporosis in Gastrointestinal Disorders
The optimum dose and duration of bisphosphonates remains unclear when continued beyond that seen in clinical trials. Some physicians offer stable or moderate-risk patients a 1-year holiday after 5 years of alendronate therapy based upon the results of the cessation arm of the FLEX study.
Calcitonin Calcitonin interacts with osteoclast receptors, thereby reducing bone resorption. A 5-year trial in postmenopausal women showed a reduction of vertebral fractures at a dose of IU daily intranasally, but not at a dose of IU daily, and no effect on BMD or nonvertebral fractures. Calcitonin is used infrequently, due to the availability of more potent alternatives. Teriparatide Teriparatide or the amino acid fragment of human recombinant parathyroid hormone rhPTH is the only directly anabolic agent approved for the treatment of osteoporosis.
Daily subcutaneous dosing of PTH is anabolic on osteoblasts compared to continuous endogenous hyperparathyroidism, which causes bone loss. In the pivotal fracture trial, teriparatide therapy significantly increased BMD and reduced fractures compared to placebo.
When compared to alendronate for the treatment of GCS-induced osteoporosis, teriparatide resulted in larger increases in BMD.
The exact mechanism of action remains unclear. Strontium has not been approved for use in the United States. Newer SERMs may offer improved fracture protection. It was highly effective in postmenopausal osteoporosis 71 and has recently been approved by the FDA for treatment of postmenopausal women at high risk for fractures.
Osteoporosis and Gastrointestinal Disease
Ongoing studies in oncology patients include the use of denosumab to treat the effects of androgen deprivation therapy for prostate cancer 72 and for treatment of skeletal metastases. Common causes of back pain include strains to the muscles or ligaments, bulging or ruptured discs between the vertebrae in the spinearthritis, skeletal irregularities like scoliosis, or osteoporosis. Rarely, back pain can signal a serious condition, and immediate medical attention should be sought for back pain that is accompanied by a fever, follows a fall or injury, or back pain that causes a new bowel or bladder problem.
For those with IBS, a new bowel problem with back pain would be different than their usual symptoms. If you are unsure whether your bowel problem is related to your back pain, consult your doctor.
Referred pain occurs when the perception of where pain is felt is distant from the actual cause of pain. The internal organs can often refer pain to other sites, so it is possible for pain caused by IBS to be referred to the back. The study authors noted that people with gastrointestinal symptoms may have viscerosomatic hyperalgesia, an increased sensitivity to pain in the abdomen which is believed to be the result of alterations in the brain-gut pathway.
While fibromyalgia pain can occur throughout the body, the back can be affected by pain. In a Japanese population, 25OH-vitamin D levels were lower in patients with long time of disease and in those in which the disease was active for long periods Regarding osteoporosis, 25OH-vitamin improves lower limbs function and body balance, decrease falls 59 and prevent fractures As discussed, 25OH-vitamin D deficiency can induce secondary hyperparathyroidism and increase bone turnover and resorption.
In addition to calcium malabsorption, a large number of patients with IBD do not have an adequate intake of calcium 61 Furthermore, diarrhea may lead to magnesium deficiency contributing to calcium malabsorption. Although less studied, vitamin K sufficiency is also important for bone health. Vitamin K induces bone formation and mineralization as well as accumulation of collagen into osteoblasts.
Besides bone formation, vitamin K is able to increase the production of OPG and alkaline phosphatase by osteoblasts, and induces the carboxylation and activation of osteocalcin, a protein produced by osteoblasts involved in bone mineralization.
In addition to bone formation, vitamin K can inhibit bone resorption and osteoclastogenesis. However, there is no enough clinical evidence to support the use of vitamin K to improve the bone mass and prevent fractures neither in IBD or in the general population It is controversial whether IBD per se is able to decrease the bone mass and increase fracture incidence in clinical studies.
The only clinical factor related with overall risk of fractures was age. Exposure to GC and intestinal resections were not associated with higher risk of fractures Also, the fracture risk was increased by 2. The inclusion of clinical risk factors independent associated with fracture risk Table 1 can also predict the fracture risk without using BMD values However, the risk of other osteoporotic fractures combined was related to low BMD and clinical factors, without differences determined by the presence or absence of IBD Overall, these data suggest that IBD confers a small independent risk of fractures, probably more evident in patients with severe disease.
The combination of other clinical factors may have a greater role in the pathogenesis of fractures in the IBD population. Table 1 Clinical risk factors for osteoporosis and fractures 75 - 77 Full table Bariatric surgery with intestinal bypass Surgeries that involve intestinal bypass were developed to produce malabsorption and weight loss.
RYGB is a gastrojejunostomy and consists in the creation of a small gastric pouch attached to a transected jejunum that connects to a duodenal limb Data regarding the effects of biliopancreatic diversion with duodenal switch BPDDS on bone metabolism are scarce.
In this surgical procedure, there is a partial vertical gastrectomy with preservation of the pylorus which is connected to an alimentary limb; and a long limb bypass with a portion of the duodenum attached to the pancreas and gallbladder is connected to a short common duct closer to the large intestine 80 Many authors have shown BMD loss after bariatric surgery 83 - In a RYGB prospective study with 1 year of follow-up, decreases of 9.
There was a strong correlation between BMD reduction and magnitude of weight loss. No changes occurred at spine and forearm BMD In another study, the risk of fractures was studied in patients from Olmsted County, Minnesota, who underwent bariatric surgery. The average follow-up was almost 9 years; patients were young, with a mean age of 44 years.
The risk was 2-fold higher for osteoporotic fractures forearm, vertebra and femur and 2. Many causes play a role in the pathogenesis of metabolic bone disease after bariatric surgery. There are reports of increased bone remodelling after surgery. Studies have demonstrated elevated levels of markers for bone turnover in the post-operatory period, mainly of the bone resorption indicator N-telopeptide 86 The drastic and fast reduction of BMI leads to decreased mechanical load on the skeleton, an established cause for losing BMD and muscle mass 89 Calcium and 25OH-vitamin D absorption decrease early after the surgery 86 and seems to be worse in procedures with longer Roux limbs Indeed, those patients usually need higher doses of elemental calcium due to duodenal and proximal jejune bypass, and supra physiological doses of 25OH-vitamin D to avoid secondary hyperparathyroidism Irritable bowel syndrome Few authors have investigated the association between irritable bowel syndrome IBS and risk of fractures.
Osteoporosis in gastrointestinal diseases
The authors discussed that a possible cause for osteoporosis in patients with IBS is the elevated levels of serotonin produced by the gastrointestinal tract. Besides, patients with IBS may avoid products with lactose because of gastrointestinal symptoms, limiting the intake of calcium Table 2 summarizes the etiological factors for osteoporosis secondary to GID.
Table 2 Summary of etiological factors present in gastrointestinal involved in bone disease Screening Celiac disease There is no consensus among societies regarding measurement of DXA for osteoporosis screening in CD. The British Society of Gastroenterology recommends DXA for those at higher risk of osteoporosis, with 2 or more risk factors: If osteopenia or osteoporosis is identified, specific treatment for bone disease should be offered, as suggested by the guidelines e. If BMD is abnormal without indication of treatment, its measurement should be repeated after three years.
If BMD is normal, its measurement should be repeated at menopause in women, and after year-old in males. In men with osteoporosis, testosterone levels should be checked Inflammatory bowel disease The AGA recommends that DXA scan should be performed for patients with one or more risk factors for osteoporosis Table 1which should be re-assessed in 2 to 3 years. Serum levels of calcium should be evaluated in newly diagnosed patients.
A broader investigation for secondary osteoporosis blood count, total creatinine, 25OH-vitamin D level, protein electrophoresis, and testosterone level should be done in those with osteoporosis or a previous osteoporotic fracture The British Society suggests that DXA scan should be performed in patients at higher osteoporosis risk, with at least 2 risk factors Table 1.
Other authors discuss the use of the FRAX calculator to estimate the probability of fractures and to recommend the initiation of treatment There is not enough evidence to indicate DXA scan at baseline for all patients, and the recommendation for osteoporosis screening should follow the recommendations of the National Osteoporosis Foundation www.
The measurement of 25OH-vitamin D in the preoperatory period is advised, and a more extensive investigation, including calcium, albumin, phosphate and PTH in individual patients, is suggested for those at higher risk. It is recommended to evaluate hour urinary calcium excretion at 6 months after the surgery, and then annually The prevention of fractures should follow the standards for the general population. Treatment and prevention of metabolic bone diseases Celiac disease GFD is the main treatment for bone disease associated with CD.
It improves bone mass, but may not normalize BMD in all patients. Response depends on when the GFD is implemented. Patients with untreated CD in the two first decades of life may not reach their bone mass peak.
In this situation, bone mass is unlikely to recover completely. The increment of BMD will be lower in the subsequent years It is important to emphasize that the reduction of the fracture risk in patients following the GFD is not only due to the BMD increase, but also because the overall nutritional status, body composition, BMI, and bone architecture are improved, and risk of falls is decreased The intake of 25OH-vitamin should be IU per day.
General recommendations of weight bearing exercise, alcohol and tobacco avoidance should be enforced. In patients with osteoporosis at high risk of fractures e. In men with osteoporosis and hypogonadism, testosterone should be offered Citrate is the first choice because of hypocloridria caused by gastrectomy. The aim of calcium and 25OH-vitamin D supplementation is to avoid secondary hyperparathyroidism without inducing hypercalciuria The best options are intravenous bisphosphonates zoledronate and ibandronate since the absorption of oral bisphosphonates is impaired with hypocloridria.
Also, oral bisphosphonates may cause anastomotic ulceration Conclusions GID can lead to significant impact on bone health and are frequent causes of secondary osteoporosis. Normal intestinal function is essential for an adequate calcium metabolism. Low calcium intake due to avoidance of milk and dairy products is also common in patients with GID, not only in those with malabsorption, but also in patients with disorders associated with chronic abdominal pain, altered bowel habits and abdominal bloating such as IBS and colitis ulcerative.
Calcium and vitamin D status should be analysed and supplementation ensured when necessary. Use of GC, weight loss, disease activity, systemic inflammation and immobility present in patients with GID also play roles in the pathogenesis of bone disease. There is not enough evidence to determine the independent risk of each GID for fractures. However, patients with GID frequently present multiple risk factors for bone disease.
Since osteoporosis in general progresses slowly and bone loss is not always completely reverted with treatment, a high level of suspicion is required to prevent advanced bone loss and fractures. Thus, prompt evaluation and diagnosis are important for patients at risk of bone disease.
Control of the primary GID, reinforcement of a healthy lifestyle and prescription of drugs which negatively affect bone metabolism with parsimony are good strategies to prevent bone disease. In the future, the validation of diagnostic tools, such as FRAX, in subgroups with specific GID will optimise the clinical judgement and indication of osteoporosis treatment, especially for patients who are not clearly at high risk of osteoporosis and fractures.
The author declares no conflict of interest. Osteoporosis prevention, diagnosis, and therapy. A Report of the Surgeon General. Department of Health and Human Services, Pathogenesis of bone fragility in women and men. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Bone quality—the material and structural basis of bone strength and fragility.