Osteoporosis in Gastrointestinal Diseases of Malabsorption and Inflammation



Fig. 1
A comparison of laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB). From left to right: LAGB, SG, and RYGB (Source: Smith et al. [41]. Reprinted with permission)




Restrictive Bariatric Procedures


The LAGB constricts the initial portion of the stomach, slowing down the transit of food and thereby inducing a feeling of early satiety [37]. In this fully reversible procedure, a saline-filled band is inserted around the proximal stomach and reduces the stomach cavity to 10–20 ml [42]. While the LAGB can result in 30–50 % excess body weight reduction, proximal slippage of the band necessitates revision surgery within 5–7 years of the initial operation for 25–50 % of patients. This complication, in combination with recently developed, equally effective alternatives, has made LAGB a less popular option in recent years [43, 44].

A newer surgical option known as the gastric sleeve or sleeve gastrectomy (GS) involves resection of a large section of the lateral stomach, with the remainder stapled shut. The mechanism of weight loss is primarily through reduction of gastric capacity to approximately 120 ml [45] and decreased appetite. Weight loss is gradual over 12–18 months, and significant nutrient malabsorption does not occur because there is no involvement of the small intestine. Appetite attenuation is closely related to the elimination of a portion of the abdomen responsible for the secretion of ghrelin, an anti-satiety hormone which signals the desire to continue eating.

Although initially developed as the first stage of the combined restrictive and malabsorption procedure, SG alone has successfully resulted in a 55–60 % weight loss in some studies and is now offered as a primary procedure [46]. The elimination of ghrelin and other neurohormones including glucagon-like peptide-1 may contribute to the success of GS through continued dietary compliance of patients. One benefit of all restrictive bariatric surgeries is the sparing of the proximal small bowel where many essential vitamins and nutrients are absorbed [47]. The absence of this portion of the small intestine may lead to osteoporosis in part because of lack of vitamin D. Despite the above benefits, postoperative development of gastric reflux or exacerbation of preexisting reflux after SG can be as high as 40 %. Many patients require a surgical solution to the reflux because medications, including proton pump inhibitors, are helpful yet insufficient to overcome the functional problem created by the surgery [48].


Malabsorptive Bariatric Surgeries


In contrast to the adjustable gastric band and GS interventions, the RYGB and duodenal switch circumvent moderate to large portions of the small intestine. Weight loss occurs by redirecting digested food from the stomach to distal gut, bypassing proximal portions of the small intestine that function in key nutrient absorption. Both procedures result in a “common channel” that is shared by both digested food and pancreatic enzymes; their combined action is required for nutrient absorption. The pancreatic enzymes travel through an independent pathway and link up with the food channel further along the path. Not until they come together in the common channel is any food (particularly protein) absorbed [37]. The shorter the channel, the greater the likelihood of insufficient absorption, especially if the length is less than 120 cm from the start of the channel to the ileocecal valve [47]. Certain procedures carry a higher risk of side effects than others. A summary of the complications with the three most common types of procedures is given in Table 1 [49].


Table 1
Complications associated with bariatric surgery procedures























































Procedure

Complications

Laparoscopic Roux-en-Y gastric bypass

Leaks

Anastomotic narrowing and strictures

Marginal ulcers

Jejunal ischemia

Small bowel obstruction

Internal hernias

Intussusception

Recurrent weight gain

Gastrogastric fistula

Laparoscopic adjustable gastric banding

Stomal stenosis

Malpositioned band

Pouch dilation

Distal band slippage

Perforation

Gastric volvulus

Intraluminal band erosion

Port-related and band-related complications

Laparoscopic sleeve gastrectomy

Gastric leaks

Gastric strictures and gastric outlet obstruction

Gastric dilation

Gastroesophageal reflux


Source: Levine and Carucci [49]

RYGB is synonymous with the term “gastric bypass” and results in as much as a 65 % excess body weight loss. The sleeve gastrectomy–duodenal switch combined procedure offers the greatest loss, up to 80 % of excess body weight. This is a modification of earlier versions of the biliopancreatic diversion [5053]. Even in revised form, patients can become severely malnourished, particularly in vitamin B12 levels, and must be closely followed with blood tests of fat- and water-soluble vitamins and trace elements like zinc and copper [54].

Many considerations go into the decision for surgery. The desired amount of weight to be lost for medical reasons, the risks of a given procedure to the individual patient, and the patient’s prior history with weight loss attempts must all be carefully balanced. The patient’s own commitment to preparing for the surgery medically and psychologically and their commitment to follow-up care and ongoing nutrition are as important if not more important than the actual surgical procedure chosen. Table 2 describes important selection criteria [55].


Table 2
Selection criteria for bariatric surgery

































Factor

Criteria

Weight: adults

Body mass index ≥35 kg/m2 and obesity-associated comorbidity

Body mass index ≥40 kg/m2

Weight: children

Severe comorbidity and >95th percentile of weight for age

Weight loss history

Failed attempts of nonsurgical weight loss, including profit-making commercial programs

Commitment

Expectation that patient will adhere to postoperative care including follow-up visits, recommended medical management, and recommended tests or procedures

Exclusion

Current drug or alcohol abuse

Severe, uncontrolled psychiatric illness

Reversible endocrine disorders that may lead to obesity

Inability to comprehend bariatric surgery details (benefits, risks, expected outcomes, alternatives, lifestyle changes, etc.)


Source: Mechanick et al. [55]



Nutritional Deficiencies After Surgery


Malabsorption arises in both macro- and micronutrients following bariatric surgeries. Deficits in many of the key nutrients serving to support bone structures serve as major contributing factors to the development of postsurgical osteoporosis [47]. The major macronutrient affected is protein. When reduced length of the small intestine results in inadequate time for pancreatic enzymes to act on ingested dietary protein, insufficient protein absorption occurs. Anemia and hypoalbuminemia are observed in gastric bypass and duodenal switch [47]. Generalized edema that leads to mobility deficits and severe muscle wasting may require physical therapy, in addition to nutritional correction measures such as liquid protein supplementation, to aid functional recovery. As muscle wasting progresses, patients shift stress from their muscles to their bones for ambulation and transfers. In addition, profoundly weak proximal muscles may make activities such as sit to stand transfers more challenging and an increased fall rate is predictable. If BMD is low, falls and altered stress on bones during weight-bearing activities may lead to fractures.

Micronutrients include water-soluble B and C vitamins; fat-soluble vitamins A, D, E, and K; and trace minerals such as copper and zinc. Another key mineral of concern is calcium. In assessing risk of developing bone disease, any nutrient that results in weakness, alters proprioception, causes myalgias, compromises awareness, or results in functional deficits that increase fall risk or reduce mobility warrants discussion. Vitamin B12 deficiency occurs in patients who have undergone procedures that bypass the lower stomach [37] with findings indicating inadequate B12 in 40 % of patients after the first year following traditional RYGB [56, 57]. Vitamin B12 deficiency results in pernicious anemia, affecting both the dorsal tracts of the spinal cord responsible for proprioception and vibration as well as the corticospinal tracts responsible for motor function. A severe form of Vitamin B12 deficiency compromises safety in cases of weight-bearing, ambulation, and transfers, leading to self-care deficits and an increased risk of falls.

Vitamin B1 (thiamine) deficiency arises from bypass of the jejunum where absorption occurs or from recurrent emesis, caused by reduced gastric size or stomal stenosis. Loss of thiamine can present after either gastric banding or gastric bypass [36]. Seen in 49 % of patients after RYGB [58], thiamine deficiency induces Wernicke’s encephalopathy involving nystagmus, ophthalmoplegia, confusion, and ataxia [59]. Polyneuropathy has been reported after gastric bypass [5961]. Nakamura et al. [60] emphasize that a single dose of supplemental thiamine may correct a lab reading for serum levels of vitamin B1, but if neurological deficits have occurred because the patient has gone untreated in previous months, functional deficits in the form of ataxia and gait dysfunction will remain. Electrodiagnostic studies often confirm a distal axonal sensory polyneuropathy and support the need for physical therapy to educate patients in compensatory measures that improve safety during ambulation and prevent falls [60].

Both calcium and vitamin D are absorbed from portions of the gastrointestinal tract that are bypassed in RYGB and similar malabsorptive bariatric procedures. Due to vitamin D malabsorption, calcium metabolism is compromised through a physiologic mechanism apart from the absence of absorption from the missing region of gastrointestinal tissue. A hypocalcemic state ensues and secondary hyperparathyroidism follows [47]. After gastric bypass, calcium deficiency is seen in 10–25 % of patients after one year and 25–48 % after two years. Vitamin D deficiency one year after a malabsorptive surgery ranges from 17 % to 52 % and becomes significantly worse as years pass unless treatment is initiated. In a series of investigations by Brolin, vitamin D deficiency was seen in 50 % of patients five years after surgery if they had a short common channel 75 cm from the ileocecal valve [56]. Although aggressive supplementation will be helpful in preventing further metabolic disease, this alone may be insufficient in patients with malabsorptive procedures, and dosages of 50,000 IU ergocalciferol weekly may be needed.

Although vitamin D and calcium deficiency are far more common after malabsorptive procedures than after restrictive GI surgeries, deficits in both bone density and individual nutrient deficiencies may occur nonetheless. A study of 73 adolescent patients found that four subjects (5.5 %) had vitamin D deficiency. Restrictive food intake may play a role, but because this study involved teenagers, dietary compliance may be challenging, although physician follow-up in this study was 90 %, far exceeding statistics in most adult bariatric follow-up clinics. Aarts et al. found that in a study of 60 patients who were consuming a daily multivitamin containing 400 IU vitamin D, 39 % were deficient following SG procedures [62]. In this same study, 5 % of patients had vitamin B12 deficiency and 15 % had folic acid deficiency, but what is more remarkable are the chronically elevated levels of vitamin A, B1, and B6. Findings highlight the need for comprehensive and frequent postoperative metabolic monitoring coupled with a more aggressive nutritional approach, similar to that offered to restrictive surgery patients. A simple multivitamin is far from adequate and may have an inappropriate mixture of too little vitamin D and too much vitamin A or B6. Table 3 gives suggestive preoperative nutritional assessment measures which should be reviewed with each patient prior to planning surgery [63].


Table 3
Suggested preoperative nutrition assessment













































































General

Specific

Weight history

Recent weight loss attempts

Weight gain and loss trends

Personal weight loss goals

Medical history

Comorbidities

Medications and supplements

Food allergies and intolerances

Body fat distribution

Available lab values

Dentition problems

Eyesight problems

Psychiatric history

Eating disorder history

Psychiatric diagnoses

Alcohol, tobacco, drug use

Nutrition and food

Food, mood, and activity log

Eating patterns

Restaurant meal intake

Food cravings

Cultural and religious dietary considerations

Physical activity

Current activity level

Physical conditions that limit activity

Previous enjoyment of physical activities

Time spent sedentary daily

Psychosocial

Confidence in ability to maintain weight loss

Support system, family dynamics

Motivations and reasons for wanting surgery

Willingness to comply with protocol

Emotional connection with food

Stress level and coping mechanisms

Education

Literacy level

Language barrier


Source: Allied Health Sciences Section Ad Hoc Nutrition Committee, Aills L et al. [63]


Epidemiology of Osteoporosis After Bariatric Surgery


Scibora et al. [37] have conducted comprehensive reviews of retrospective and prospective studies of osteoporosis and bone density changes related to bariatric surgeries. Because bone loss is a well-established outcome of gastrectomy for non-weight loss purposes, clinicians have long been aware of the risk of osteoporosis following bariatric surgeries [64]. Data from cross-sectional and retrospective studies of BMD in the hip, radius, and lumbar spine have been difficult to interpret due to a number of confounding issues. Obese patients typically have higher BMD than normal weight controls due to the presence of estrogen content in fat cells; thus, comparing postoperative yet still overweight gastric bypass patients to normal weight controls may present challenges. Moreover, many of the cross-sectional studies were unable to separate pre- and postmenopausal women, resulting in a heterogeneous population and compromising any conclusions for specific groups.

Prospective studies examining changes in BMD within the same individual at preoperative and postoperative time points have proven to be more valuable. Overall these investigations support decreases in BMD following malabsorptive as opposed to restrictive surgeries, with the greatest reduction seen in BMD at the hip relative to the lumbar spine or radius [37]. After restrictive surgeries in which the weight loss is less than that achieved from malabsorptive procedures, bone loss at the hip is found to vary by site and is inconsistent among studies. The femoral neck BMD declined by approximately 2.3 % one year after LAGB in a study of premenopausal women [65]. In restrictive procedures where weight loss is accomplished through constriction-forced dieting due to limited abdominal size, weight loss and bone loss continue into the second and subsequent years after surgery. A two-year study demonstrated that femoral neck BMD declined 3.5 % [65, 66]. Although vertical gastric banding is a restrictive procedure done far less frequently today, studies did find that it results in greater bone loss at the proximal hip of 10–14 % [65]. Patients now have other options which may be more favorable from a number of medical perspectives. Bone turnover markers were elevated following SG in one small-scale investigation of 15 patients indicating ongoing effects of bone loss [67].

Greater bone loss is consistently observed with malabsorptive procedures. A number of reports estimate that total bone loss at the femoral neck following either RYGB or the more aggressive biliopancreatic diversion (also now rarely performed) ranges from 9–10.9 % at the femoral neck and 8–10.5 % at the total hip. Postoperative care in the majority of bariatric surgical centers includes vitamin supplementation with vitamin D. But teams caring for patients in a postoperative setting lack a standard protocol, and the amounts that each patient receives vary by institution. In the setting of 800 IU vitamin D3 and 1200 mg daily calcium supplementation [68], femoral neck BMD one year after surgery declined by 10.9 %; in another investigation with even greater supplementation of vitamin D and calcium, BMD of the femoral neck declined by 9.2 % while the total hip saw an 8 % decrease. Since most of the weight loss occurs in the first year following RYGB, findings of stability of BMD in the second and third years following surgery are conceivable [65].

Fleischer et al. [69] assert that the degree of bone loss following restrictive procedures parallels the degree of weight loss. Their prospective study of 23 patients one year following RYGB demonstrates bone loss at the total hip of 8 % and at the femoral neck of 9.2 %. In addition, elevated markers of bone loss in the form of N-telopeptide confirm an active bone loss process. This finding is further supported by a simultaneous increase in PTH and a reduction of urinary calcium, even in patients who increased calcium and vitamin D intake postoperatively to 2400 mg and 1600 IU, respectively. This study is only one of a number of investigations [70, 71] demonstrating increases in markers of bone loss and of PTH. Bruno et al. [70] did show that supplementing patients with 1200 IU vitamin D, more than the Fleisher investigation that prescribed 600 IU for subjects under 50 and 800 IU for those over age 50, prevented development of postoperative vitamin D deficiency. However, even 1200 IU was insufficient to prevent elevation of bone turnover markers.

Bone loss in the lumbar spine is again seen more commonly in patients undergoing malabsorptive rather than restrictive bariatric procedures. After LAGB surgery, one study [66] showed a 3.5 % and 1.6 % increase in BMD, respectively. Several other investigations [7274] demonstrated either no change or a small increase that was not statistically significant. In SG, Hsin et al. [74] found no change in lumbar spine BMD between L1 and L4 after one year. In contrast, RYGB and similar malabsorptive procedures result in a reduction of lumbar BMD by 3.6–8 % in premenopausal patients, even in those who are supplemented proactively with calcium and vitamin D, the amounts of which vary by study [37, 68, 75]. More aggressive supplementation is unable to help preserve BMD in more aggressive malabsorptive procedures. Tsiftsis et al. [75] noted a 7–8 % decline in lumbar BMD after biliopancreatic diversion in 26 premenopausal women who were given 2 g of calcium daily. This group was also supplemented with vitamin D.

Quite often, bone loss and fractures can occur in nontraditional osteoporotic sites following bariatric surgery, but many of the fractures are not observed until years after surgery. In a large prospective study of 258 subjects, representing 2286 person-years, 79 individuals experienced 132 fractures. Conducted between 1989 and 2004, this investigation has one of the longest follow-up periods of published works to date. In total, 56 % of subjects experienced only one fracture, while 26.5 % reported two or more fractures. The cumulative incidence of fracture after 15 years was 58 %, with the most common mechanism of injury being a fall. However, many fractures occurred in nontraditional osteoporotic sites: 22 % in the feet or toes, 7.6 % in the ribs, and 15 % in hands or fingers [76].



Treatment for Bariatric Surgery Patients



Pharmacologic Interventions



Nutrition Supplementation


The Endocrine Society has developed specific recommendations for treatment of deficiencies anticipated after bariatric surgery, especially after malabsorption procedures, with the expectation of preventing major instances of malnutrition if supplementation is done at the beginning of postoperative care. These recommendations include taking two multivitamin tablets daily, preferably separated in time, as well as consuming 1200–2000 mg of elemental calcium and at least 1000 IU of cholecalciferol (Vitamin D3), if the individual is replete in vitamin D25OH at the time of surgery. Those with greater deficiencies would understandably need higher doses of vitamin D3 or a 50,000 IU capsule of vitamin D2 (ergocalciferol) [36]. These clinical practice guidelines further advise that if aggressive supplementation of nutrients is attempted and fails, revision surgery may be needed to avert severe malnutrition [36].

As illustrated in the prior section, supplementation with various nutrients is helpful but not sufficient in the more aggressive forms of bariatric surgery, particularly in malabsorptive procedures but also in some restrictive procedures such as SG involving the rapid and substantial loss of ghrelin. Gjessing et al. [77] found substantially elevated PTH levels and hypocalcemia one year after SG. The resultant malabsorption of calcium, in conjunction with ongoing hyperparathyroidism, contributes to osteoporosis. Through the above mechanism, supplementation with additional calcium and vitamin D appears unlikely to help. Reduction in PTH and downregulation of osteoclasts or upregulation of osteoblasts may need to be approached from a different direction. Interestingly, Hsin et al. [74] used the guidelines developed by the AGA in his study, and with the exception of the lumbar spine BMD, many regions of the skeleton nonetheless experienced extensive bone loss following bariatric procedures.


Emerging Concept of Bariatric Osteomalacia


A number of studies looking at postmenopausal osteoporosis rarely find that vitamin D or calcium alone can have a singular impact on the development of osteoporosis. However, the situation is very different for those who have experienced malabsorptive bariatric procedures, with results demonstrating the positive impact of aggressive supplementation with calcium citrate and cholecalciferol. Williams [78] describes a case of one female who originally had low BMD in her radius but after eight months of aggressive supplementation achieved a 55 % improvement of BMD. Following treatment, she experienced no further development of calcium oxalate stones and reported less muscle and bone pain together with better endurance and strength.

The pattern of bariatric osteomalacia can be so profound that myopathy as well as peripheral neuropathy can develop. A number of case reports describe these events, which can have a devastating effect on a patient’s level of independence. Such cases require astonishingly large doses of vitamin D (in one case 1200 IU orally daily plus 400,000 IU intramuscularly every month) to realize improvement in lab values following SG and RYGB [7981].


Medications


Because oral bisphosphonates carry a high risk of gastrointestinal reflux, these agents are largely contraindicated after bariatric procedures. In fact, reflux is one of the most common adverse effects following SG and a number of malabsorptive procedures. Bisphosphonates and NSAIDs are two classes of drugs that have been specifically reported to worsen symptoms [78]. Intravenous bisphosphonates, subcutaneous denosumab, or other oral medications without side effects of gastric reflux are worth discussing, but few reports examining these alternatives have been published outside of limited case studies. Oral alendronate was used successfully in one small investigation of 13 patients who had undergone one of several types of gastrectomy for gastric cancer, one being RYGB with the others being Billroth I and II and partial as well as total gastrectomy [82]. No reports exist for treatment with intravenous zoledronic acid, but one article does describe two cases of pamidronate used effectively for treating immobilization hypercalcemia in the postoperative period following RYGB [83]. The two subjects described by Alborzi and Leibowitz required direct ICU admission from home following RYGB for dangerously elevated serum calcium levels which were attributed to a combination of inactivity postoperatively, specifically reduced weight-bearing on a skeleton which had been used to carrying significant amounts of weight, and disruption of the calcium homeostatic axis which indirectly elevates osteoclastic activity. In the above cases, pamidronate was found to be safe and effective for hypercalcemia. Although its benefit for osteoporosis prevention has not been investigated, the initial safety data from the above case reports are encouraging.

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Aug 17, 2017 | Posted by in PHYSICAL MEDICINE & REHABILITATION | Comments Off on Osteoporosis in Gastrointestinal Diseases of Malabsorption and Inflammation
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