Metabolic Bone Disease After Bariatric Surgery
Obesity was originally felt to strengthen bone because of the long-term weight-bearing burden on bone. However, more recent evidence suggests that obesity may not be as protective on bone health. Factors which contribute to the site-specific fracture risk in obesity include adipokine effects on bone physiology, systemic inflammation, reduced mobility, and vitamin D deficiency.
The prevalence of vitamin D deficiency in individuals with obesity varies from 20% to 85%. Mechanisms include lack of sufficient sun exposure to convert 7-dehydrocholesterol (7-DHC) to vitamin D3
and sequestration of vitamin D in adipose tissue.15
In patients with overweight and obesity, modest weight loss has been shown to result in small decreases in bone density of the hip with sparing of the spine. With greater degree of weight loss, metabolic and bariatric surgery is associated with a deterioration in bone health with specific effects shown in Table 10.1
TABLE 10.1 Clinical Findings Showing the Deterioration in Bone Health After Metabolic Surgery
EFFECTS OF METABOLIC SURGERY ON BONE HEALTH
Alterations in bone remodeling with increase in markers of remodeling
Increased rates of bone loss
Bone loss by quantitative imaging (DEXA)
Alterations in bone strength
Microarchitectural deterioration related to increased PTH levels
Increase in fracture risk with time after surgery
DEXA, dual-energy x-ray absorptiometry; PTH, parathyroid hormone.
Due to greater malabsorption, the RYGB
procedures are associated with the greatest risk of bone loss and fracture risk compared to the SG or the AGB
. The pathogenesis of bone loss after metabolic and bariatric surgery is multifactorial. Malabsorptive surgery results in reduced intestinal absorption of calcium and vitamin D. Reduced gastric acid production related to surgery and antacid use will further reduce calcium absorption, leading to hypocalcemia which is a stimulus for parathyroid hormone (PTH
) release and a diagnosis of secondary hyperparathyroidism. This in turn increases bone loss. Evidence also suggests that bone loss after bariatric surgery correlates with the amount of weight loss and the rate at which it occurs due to increased activation of the calcium-PTH axis. Surgery has also been shown to increase the bone turnover markers, N-terminal telopeptide of type I collagen (NTX), bone-specific alkaline phosphatase (BSAP), and osteocalcin. One important marker, sclerostin, is produced in osteocytes, and its main function is to inhibit bone formation. Mechanical unloading of bone after weight loss has been associated with an increased level of sclerostin resulting in significant loss in bone mineral density (BMD). Monitoring of bone health in postoperative patients undergoing all types of bariatric procedures is critical for its preservation. Guidelines for monitoring are summarized in Table 10.2
Biochemical indices for diagnostic testing for metabolic bone disease include serum calcium, phosphorus, magnesium, 25(OH)D (and 1,25(OH)D if renal function is compromised), BSAP or osteocalcin, PTH
, and a bone marker of resorption such as urine n-telopeptide (NTX), 24-hour urinary calcium excretion, and albumin and prealbumin. Routine monitoring should include only PTH
, 25(OH)D every 3 to 6 months for the first year and annually thereafter for patients undergoing AGB
, SG, or RYGB
. For those who have undergone BPD
with or without switch, the following are recommended: PTH
and 24-hour urine calcium monitoring every 6 to 12 months, urine N-telopeptide annually, and osteocalcin as needed3
TABLE 10.2 Laboratory Screening and Monitoring for Bone Health After Surgery
GUIDELINES FOR MONITORING BONE HEALTH AFTER METABOLIC SURGERY
Laboratory tests used in the evaluation of bone health
Calcium, phosphorous, magnesium
25(OH) vitamin D (and 1,25(OH) vitamin D if renal function is impaired)
Bone-specific alkaline phosphatase or osteocalcin
Parathyroid hormone (PTH)
24-hour urinary calcium excretion
Vitamin A and K1 levels
DEXA at baseline and 2-year follow-up
DEXA, dual-energy x-ray absorptiometry.
Dual-energy x-ray absorptiometry (DEXA) is the gold standard for measuring bone density; the results are reported in T- and Z-score. The Z-score should be used for premenopausal women and men younger than 50 years. This score is the patient’s BMD expressed in standard deviations (SDs) from the mean in an age- and sex-matched reference population. A low Z-score (below -2.0) is a concern for less bone mass compared to similar aged matched individual. Whereas the T-score is also calculated as an SD from the mean, the comparison group is that of young healthy adults. The World Health Organization (WHO
) classifies T-scores above -1 SD as normal, between -1 and -2.5 SD as osteopenia, and below -2.5 SD as osteoporosis. Guidelines recommend DEXA 2 years postoperatively for both men and women after any type of metabolic and bariatric surgery. HCPs should evaluate each postoperative surgical patient based on risk factors which include age, baseline vitamin D and PTH
status, weight loss trajectory, and activity level for decisions related to assessment of bone density.17
An abnormal DEXA scan may be indicative of both primary and secondary disease. In the post-bariatric
surgery patient, one should first suspect secondary bone disease due to nutritional deficiencies. The etiology of confirmed vitamin D deficiency, hypocalcemia, hypomagnesemia, hypophosphatemia, elevated alkaline phosphatase, secondary hyperparathyroidism, and even protein or vitamin B12 deficiency should be clearly defined and appropriately treated. Treatment should also include weight-bearing exercise and resistance training to mitigating bone loss after surgery.
TABLE 10.3 Routine Monitoring for Metabolic Bone Disease for Bariatric Surgery Patients
BPD w/wo DS
Every 3-6 months for the first year and annually thereafter:
DEXA monitoring may be indicated at baseline and at about 2 years
Every 3 months for the first year, every 3-6 months thereafter:
Every 6-12 months:
Parathyroid hormone (PTH) 24-hour urine calcium
DEXA monitoring may be indicated at baseline and at about 2 years
BPD w/wo DS, biliopancreatic diversion with or without duodenal switch; DEXA, dual-energy x-ray absorptiometry; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy.
For treatment of vitamin D deficiency, The Endocrine Society recommends a dose two to three times higher (6,000 to 10,000 IU/day) for patients with obesity, patients with malabsorptive syndromes, and patients on medications affecting vitamin D metabolism. A maintenance therapy of at least 3,000 to 6000 IU/day is recommended. Correction of vitamin D deficiency in bariatric surgery patients generally requires higher doses, particularly in the malabsorptive procedures. Repletion has been recommended for as high as 50,000 to 150,000 IU of D2 or D3 daily for one to 2 weeks. A maintenance dose of up to 50,000 IU one to three times per week may be required. Cholecalciferol (D3) has demonstrated superiority at maintaining 25(OH)D levels and has been recommended particularly if dosing is less than once weekly. It is recommended that both D2 and D3 be taken with a meal containing some fat to maximize absorption.
For patients with persistently low bone density on DEXA with clinical and biochemical evidence of bone disease, additional pharmacologic treatment with a bisphosphonate should be considered. Current recommendations include intravenous therapy with zoledronic acid, 5 mg once a year, or ibandronate, 3 mg every 3 months, due to higher risk of anastomotic ulceration and decreased absorption in RYGB
patients. Patients without concerns for risk of ulceration or lack of absorption can be supplemented by mouth using alendronate 70 mg/week, risedronate 35 mg/week (or 150 mg/month), or ibandronate 150 mg/month.
Nephrolithiasis After Bariatric Surgery
An increase in the incidence of nephrolithiasis after metabolic and bariatric surgery has been clearly established, particularly in BPD
patients, where the calcium oxalate stone risk is threefold that of age-matched controls. A recent study also revealed a 7.6% incidence of nephrolithiasis after any bariatric surgery with a post-RYGB kidney stone incidence at 8.1%. Stone development after malabsorptive (BPD
) and restrictive (SG) bariatric procedures are largely caused by changes in 24-hour urine profiles, such as increased urinary oxalate, decreased urine volume, and reduced urinary citrate levels leading to increased risk of kidney stones.18
Increased oxalate absorption and a hyperoxaluric state is facilitated by increased colonic oxalate related to increased colonic fatty acid and bile salts as well as alterations in the gut microflora.
The most important factor in preventing stone formation is increasing fluid intake since a greater urinary volume provides a dilutional effect leading to decreased supersaturation ratios. Patients should strive to maintain a daily urine production of at least 2 L by increasing fluid intake, limit dietary oxalate (<150 mg/day) and fat intake (<40 g/day), and consume the Recommended Daily Allowance of calcium (1,000 to 1,200 mg/day).19
Supplemental calcium is also recommended as it binds oxalate, leading to excretion in feces. Postoperative patients who develop symptomatic stones should have an evaluation and intervention by a urologist.
Postprandial Hyperinsulinemic Hypoglycemia
An important unintended metabolic complication which has become increasingly recognized is postprandial hyperinsulinemic hypoglycemia (also called post-bypass hypoglycemia or PBH
), which is characterized by hypoglycemic symptoms developing 1 to 3 hours after a meal, in association with a low blood glucose level of <54 mg/dL and relieved by the ingestion of carbohydrate. PBH
is distinct from a condition called dumping syndrome where vasomotor symptoms occur within minutes to 1 hour after a meal of calorie-dense food, caused by rapid hyperosmotic food entry into the jejunum which induces fluid shifts into the small intestine.20
Dumping usually occurs early after surgery, most commonly after RYGB
, whereas classic PBH
commonly develops between 1 and 4 years after surgery.
has become increasingly recognized, additional studies with larger patient numbers suggest that this condition is most commonly associated with RYGB
but has been described after BPD
with DS and GS as well. The exact prevalence of this disorder remains unclear, but with increased number of patients undergoing bariatric surgeries, HCPs will likely encounter such patients.
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