Increased PTH and 1.25(OH)(2)D levels associated with increased markers of bone turnover following bariatric surgery

Abstract

The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH)(2)D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH)(2)D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)(2)D levels and increased bone turnover markers.

Figure 1

Percent change (reported as median values) in serum 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)₂D), and parathyroid hormone (PTH) at postoperative months 3, 6, 9, 12, and 18 compared to baseline. (a) 25OHD: 25OHD levels increased significantly from baseline starting at month 3. As the study progressed, 25OHD remained elevated from preoperative levels, but the magnitude of the increase diminished. (b) 1,25(OH)₂D: Serum 1,25(OH)₂D levels began to increase at 3–6 months, but this increase did not become significant until 12 months. (c) PTH: PTH initially decreased significantly at 3 months, but began to approach and eclipse preoperative levels thereafter.

Figure 2

Percent change (reported as median values) in bone turnover markers at 3, 6, 9, 12, and 18 months compared to baseline. (a) Urinary N-telopeptide (U-NTx) (a marker for bone resorption), and (b) osteocalcin (a marker for bone formation). Markers for both bone resorption and formation became significantly elevated from baseline at 3 months and remained elevated through 18 months.