Obesity Surgery, 14, 1222-1226
Elevated Serum Parathormone after Roux-en-Y
Gastric Bypass
Maria de Fátima Haueisen Sander Diniz, MD1; Marco Túlio Costa Diniz,
PhD2; Soraya Rodrigues Almeida Sanches, PhD2; Patrícia Paz Cabral de
Almeida Salgado, MD1; Maristane Mendes Andrade Valadão, MD1; Flávia
Caldeira Araújo3; Daniele Siríaco Martins3; Alexandre Lages Savassi
Rocha, MD2
1Serviço
de Endocrinologia e Metabologia, 2Instituto Alfa de Gastroenterologia, 3Medical student,
Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Background: Abnormalities in calcium and vitamin D
metabolism are observed early after gastric bypass,
whereas clinical or biochemical evidence of metabolic bone disease might not be detected until many
years after the procedure. The aim of the present
study was to evaluate the impact of bariatric surgery
on bone metabolism determined on the basis of postoperative laboratory changes in calcium, phosphorus, magnesium, alkaline phosphatase and parathormone (PTH) levels.
Methods: 110 patients submitted to Roux-en-Y gastric bypass (RYGBP) were followed after surgery, and
the following parameters were determined: intact PTH
molecule (PTHi; chemiluminescence), alkaline phosphatase (colorimetric method), ionic calcium (selective electrode), phosphorus and magnesium (colorimetric method).
Results: Elevated serum PTHi levels were observed
in 29% of the patients and hypocalcemia in 0.9% from
the 3rd postoperative month and afterwards (3 to 80
months after surgery).
Conclusion: There is a need for careful evaluation
of bone metabolism and for routine calcium replacement after RYGBP.
Key words: Morbid obesity, gastric bypass, parathyroid
hormone, metabolic bone disease, calcium metabolism
Reprint requests to: Maria de Fátima Haueisen Sander Diniz,
MD, Departamento de Clínica Médica da Faculdade de Medicina
da UFMG. Av Alfredo Balena, 110 4˚ andar 30130-100, Belo
Horizonte, Minas Gerais, Brazil. E-mail: mfhsdiniz@ufmg.br
1222
Obesity Surgery, 14, 2004
Introduction
The prevalence of overweight and obesity has been
increasing in epidemic proportions in the western
world, including morbid obesity. The World Health
Organization emphasizes the need for obesity prevention and management strategies adapted to each
local situation. Class III morbid obesity is accompanied by a significant increase in morbidity and mortality, mainly due to cardiovascular causes.1 The
quality of life of massively obese individuals is
comparable to that of a patient with severe cirrhosis
of the liver.2 In terms of public health, the high cost
of treatment of co-morbidities associated with morbid obesity supports the need for effective treatments for weight loss.
Numerous epidemiological studies have confirmed the improvement, or even resolution, of comorbidities associated with morbid obesity, after
weight loss.3,4 However, the prolonged efficacy of
dietetic and pharmacological treatments for class III
obese individuals does not exceed 10%. Within this
context, bariatric surgery is the most effective therapeutic modality for weight loss and maintenance in
the long term.5 However, the postoperative complications of this procedure justify a rigorous followup of these patients. Because the most frequently
employed surgical techniques combine restrictive
effects and malabsorptive mechanisms, nutritional
© FD-Communications Inc.
Elevated PTH after RYGBP
deficiencies become a constant concern.6-8
Abnormalities in calcium and vitamin D metabolism start early after bariatric surgery.9 However,
clinical or biochemical evidence of metabolic bone
disease may not be detected until many years after
the procedure.10,11 Osteometabolic diseases found in
operated patients include secondary hyperparathyroidism, osteoporosis and osteomalacia, with secondary hyperparathyroidism generally preceding
the other disorders.12
The aim of the present study was to evaluate the
impact of bariatric surgery on bone metabolism
determined on the basis of laboratory changes in
calcium, phosphorus, magnesium, alkaline phosphatase and parathormone (PTH) during the postoperative period in patients submitted to Roux-en-Y
gastric bypass (RYGBP).
Materials and Methods
Included in the study were class III obese patients
(body mass index BMI ≥40 kg/m2)1 attended within
the Brazilian public health system, who underwent
RYGBP by the Capella technique13 between
January 1996 and January 2003 at the University
Hospital of the Federal University of Minas Gerais
(HCUFMG), Brazil. The selection criteria for
bariatric surgery were those recommended by international consensus.14,15 After providing detailed
information about the study, informed consent was
obtained from all patients before surgery.
Patients taking drugs such as glucocorticoids,
which are known to interfere with bone metabolism,
were excluded from the study.
After RYGBP, patients were followed-up at the
Endocrinology Service every 3 months until the
12th month and every 6 months thereafter. Serum
was colleted in the fasting state for the assay of:
ionic calcium (selective electrode, Roche OMNIC);
intact PTH molecule (PTHi, chemiluminescence Immulite® 1000 Systems, DPC); phosphorus, magnesium and alkaline phosphatase (colorimetric
method - OrthoClinical Diagnostics, Johnson and
Johnson). All biochemical analyses were performed
at the University Hospital.
The criterion established for analysis was an alteration in PTHi levels above 60 pg/ml during postop-
erative follow-up. The means and medians of the
results of the collected examinations were calculated.
Results
A total of 110 patients, 86 (78.2%) women and 24
(21.8%) men, were followed-up. Of these, 32
patients showed PTHi levels above 60 pg/ml, corresponding to 29% of the total sample. Among the
patients with elevated PTHi, 28 (87.5%) were
females. The mean age of the patients was 40 years
(range 20-60, median 41.3 years). The mean time
that elapsed between surgery and the detection of
elevated PTHi was 41.5 months (range 3-80, median
29.1 months). PTHi levels and postoperative period
were not correlated: there were no differences in
PTHi levels in the early versus later postoperative
periods (Pearson r=0.08).
Hypocalcemia on the occasion of PTHi elevation
was observed in one patient (0.9% of the total sample or 3.1% of patients with elevated PTHi). Table 1
summarizes the laboratory findings. Serum PTHi
levels ranged from 62 to 147 pg/dl. Thirteen patients
(40.6%) presented PTHi between 60 and 80 pg/dl,
12 patients (38%) had levels between 81 and 100
pg/dl, and 7 patients had levels >101 pg/dl. Figure 1
shows the percent distribution of patients according
to the intensity of PTHi elevation. Elevated alkaline
phosphatase was observed in two patients (1.8% of
the total sample). None of the patients showed
hypomagnesia concomitantly with PTHi elevation.
Table 1. Laboratory findings for the 32 patients with elevated intact parathormone during the postoperative
period
Range
Mean ±SD Median
Parathormone
(7-53 pg/dl)
62-147 91.2 ± 12.8
Ionic calcium
(1.12-1.32 mmol/l) 0.95-1.32 1.21 ± 0.07
Phosphorus
(2.5-4.5 mg/dl)
2.7-4.6
3.7 ± 0.0
Magnesium
(1.6-2.3 mg/dl)
1.6-2.3
2.0 ± 0.06
Alkaline phosphatase
(38-126 U/l)
61-133
87.8 ± 7.0
104.5
Obesity Surgery, 14, 2004
1.2
3.6
1.9
97
1223
Diniz et al
60-80pg/dl
81-100
>100
22%
40%
38%
Figure 1. Distribution of patients according to PTHi serum
levels.
None of the patients with elevated PTHi reported
diarrhea or steatorrhea during the postoperative
period.
Discussion
Metabolic bone disorders represent complications
of digestive surgeries, but are frequently underdiagnosed. Zittel et al16 found a high prevalence of alterations in bone metabolism, including secondary
hyperparathyroidism, during long-term follow-up of
60 gastrectomized patients.
Secondary hyperparathyroidism associated with
bariatric surgery has a multifactorial etiology,
including inadequate ingestion of calcium during
the postoperative period, malabsorption of calcium
and vitamin D, and the formation of insoluble calcium salts due to steatorrhea.17 Calcium is mainly
absorbed in the duodenum and proximal jejunum,
regions which remain excluded during gastric
bypass. In addition, hypochlorhydria reduces the
absorption of ingested calcium. In contrast, vitamin
D is absorbed in the small intestine with the help of
biliary salts; however, no specific area exists for its
absorption. Calcium deficiency stimulates the secretion of PTH. This compensatory response permits
the maintenance of normal serum levels of this ion
at the expense of calcium mobilization from
bone.9,18 The intensity of the PTH response probably depends on the amplitude of variation in calcemia and the velocity at which serum calcium is
modified. This occurs in such a way that slow
decreases in calcemia cause a moderate PTH
1224
Obesity Surgery, 14, 2004
response.18 In the population studied here, only one
patient showed hypocalcemia on the occasion of
PTHi elevation (0.9%). However, we may assume
that more frequent measurements of calcium would
permit the detection of hypocalcemia in a larger
number of cases. In the survey of Brolin and Leung6
involving various bariatric surgeons, the prevalence
of calcium deficiency after RYGBP was estimated
to be 3%.
We know that serum calcium measurements are
not good markers of postoperative calcium deficiencies. These levels are maintained stable at the
expense of mobilization from bone. Moreover, secondary hyperparathyroidism demonstrates a late
consequence of calcium deficiencies.
The incidence of secondary hyperparathyroidism
after gastric bypass is still unknown, and studies
have reported discordant results regarding calcium
metabolism in patients submitted to different types
of bariatric surgery.7,9,11,17,19,20 Rhode and
MacLean,19 following 56 patients submitted to
RYGBP for 3 to 5 years, reported elevated PTH in
14%. Amaral21 observed an increase in alkaline
phosphatase in 34% of patients submitted to
RYGBP, suggesting vitamin D deficiency.
Alterations in calcium and vitamin D metabolism
have been well recognized after biliopancreatic
diversion (BPD) and jejunoileal bypass (JIB).20,22-24
In the follow-up of 82 patients submitted to BPD,
Newbury et al20 reported an increase in PTH in
63.1% and vitamin D deficiency in 50%. Elevated
PTH levels have been observed in 30% and 17% of
patients after BPD and JIB, respectively.21 Hamoui
et al23 found an increase in PTH in 42% and 13.3%
of patients submitted to duodenal switch operation
with common channel lengths of 75 cm and 100 cm,
respectively.
Calcium and vitamin D supplementation has been
routinely standardized for BPD and JIB, while no
consensus exists regarding the routine use of calcium after RYGBP. In a recent review, Stocker7 did
not consider calcium deficiency to be significant
after RYGBP. Some authors, such as Amaral,21 recommend calcium replacement, considering that an
increase in alkaline phosphatase suggests subclinical bone disease. In addition, because many patients
are women of fertile age who are more prone to
osteoporosis and fractures during the climacteric
period, calcium replacement is well indicated.21
Elevated PTH after RYGBP
Eddy25 observed a 25% incidence of osteomalacia
during the prolonged follow-up of patients submitted to gastrectomy, with the subjects presenting
bone pains and increased alkaline phosphatase levels. In the present study, two patients (1.8% of the
total sample) showed a discrete increase in alkaline
phosphatase. Coates et al26 demonstrated the
increase in bone resorption associated with loss of
bone mineral content early after laparoscopic
RYGBP. Supplementary calcium and vitamin D was
protective against hyperparathyroidism and vitamin
D deficiency.26
Alterations in bone metabolism and vitamin D
deficiency have been described in morbidly obese
individuals even before bariatric surgery.27-29 In our
personal experience, some patients present elevated
PTHi before surgery, accompanied by low renal calcium excretion and improvement after oral calcium
supplementation (unpublished data).
On our service, a calcium-rich diet and a daily
polyvitamin, containing 162 mg calcium (calcium
citrate) and 400 IU vitamin D, were prescribed to all
patients, who are also encouraged to practice physical activities in the sun. Extra supplements of calcium were not prescribed. These recommendations
were insufficient to maintain normal PTH levels in
29% of the patients operated. According to Brolin
and Leung,6 the vitamin and mineral concentrations
present in polyvitamins are insufficient to prevent
deficiencies after surgery. Furthermore, the patients
studied belonged to a low-income population
attended by the public health system. The monthly
cost of calcium-rich diets and polyvitamins is high
in Brazil (polyvitamin cost corresponds to 10% of
the minimum wage of Brazilian people), a fact leading to low compliance with the prescriptions. We do
not have the accurate percentage of patients who are
compliant in taking the multivitamins prescribed
daily.
Despite its limitations, the present study demonstrates the need for routine calcium replacement
after RYGBP and careful evaluation of bone metabolism during the postoperative period. Therefore,
continuous follow-up of patients submitted to
bariatric surgery is fundamental, since bone alterations may occur late and can be severe.11,18
References
1. World Health Organization. Obesity: preventing and
managing the global epidemic. Report of a WHO
Consultation on Obesity, Geneva, June 1997.
2. Karlsson J, Sjöstrom L, Sullivan M. Swedish obese
subjects (SOS) – an intervention study of obesity.
Two-year follow-up of health-related quality of life
(HRQL) and eating behavior after gastric surgery for
severe obesity. Int J Obes 1998; 22: 113-26.
3. Buffington CK, Cowan Jr GSM. Gastric bypass in the
treatment of diabetes, hypertension, and lipid/
lipoprotein abnormalities of the morbidly obese. In:
Deitel M, Cowan Jr GSM, eds. Update: Surgery for
the Morbidly Obese Patient.
Toronto: FD
Communications Inc 2000: 435-49.
4. Schauer PR, Ikramuddin S, Gourash W et al.
Outcomes after laparoscopic Roux-en-Y gastric
bypass for morbid obesity. Ann Surg 2000; 232: 51529.
5. Albert M, Spanos C, Shikora S. Morbid obesity: the
value of surgical intervention. Clin Fam Pract 2002; 4:
447-54.
6. Brolin RE, Leung M. Survey of vitamin and mineral
supplementation after gastric bypass and biliopancreatic diversion for morbid obesity. Obes Surg 1999; 9:
150-4.
7. Stocker DJ. Management of bariatric surgery patient.
Endocrinol Metabol Clin North Am 2003; 32: 43757.
8. Forse RA, O’Brien A. Nutritional guidelines after
bypass surgery. Curr Opin Endocrinol Diabetes 2000;
7: 236-9.
9. Grace DM. Metabolic complications following gastric
restrictive procedures. In: Deitel M, ed. Surgery for
the Morbidly Obese patient. Philadelphia: Lea &
Febiger 1989: 339-50.
10.Crowley LV, Seay J, Mullin G. Late effects of gastric
bypass for obesity. Am J Gastroenterol 1984; 79:
850-60.
11.Mason EE. Bone disease from duodenal exclusion.
Obes Surg 2000; 10: 585-6.
12.Stein E, Shane E. Secondary osteoporosis.
Endocrinol Metabol Clin North Am 2003; 32: 115-34.
13.Capella RF, Capella JF, Mandac H et al. Vertical
banded gastroplasty - gastric bypass. Obes Surg 1991;
7: 389-95.
14.Gastrointestinal surgery for severe obesity. National
Obesity Surgery, 14, 2004
1225
Diniz et al
Institutes of Health Consensus Development
Conference Draft Statement. Obes Surg 1991; 1: 25765.
15.American Society for Bariatric Surgery, Standards
Committee. Guidelines for reporting results in
bariatric surgery. Obes Surg 1997; 7: 521-2.
16.Zittel TT, Zeeb B, Maier GW et al. High prevalence of
bone disorders after gastrectomy. Am J Surg 1997;
174: 431-8.
17.Goldner WS, O'Dorisio TM, Dillon JS et al. Severe
metabolic bone disease as a long-term complication
of obesity surgery. Obes Surg 2002; 12: 685-92.
18.Houillier P, Pailard M. Physiologie des parathyröides.
In: Encycl Méd Chir, Endocrinologie-Nutrition. Paris:
Editions Techniques 1992: 10-011-C-10.
19.Rhode BM, MacLean LD. Vitamin and mineral supplementation after gastric bypass. In: Deitel M,
Cowan Jr GSM, eds. Update: Surgery for the
Morbidly
Obese
Patient.
Toronto:
FDCommunications Inc 2000: 161-9.
20.Newbury L, Dolan K, Hatzifotis M et al. Calcium and
vitamin D depletion and elevated parathyroid hormone following biliopancreatic diversion. Obes Surg
2003; 13: 893-95.
21.Amaral JF, Thompson WR, Caldwell MD et al.
Prospective metabolic evaluation of 150 consecutive
patients who underwent gastric exclusion. Am J Surg
1984; 147: 468-76.
1226
Obesity Surgery, 14, 2004
22.Marceau P, Hould FS, Lebel S et al. Malabsorptive
obesity surgery. Surg Clin North Am 2001; 81: 111327.
23.Hamoui N, Kim K, Anthone G et al. The significance
of elevated levels of parathyroid hormone in patients
with morbid obesity before and after bariatric surgery.
Arch Surg 2003; 138: 891-7.
24.Vage V, Gjesdal CG, Eide GE et al. Bone mineral density in females after jejunoileal bypass: a 25-year follow-up study. Obes Surg 2004; 14: 305-12.
25.Eddy RL. Metabolic bone disease after gastrectomy.
Am J Med 1971; 50: 442-50.
26.Coates PS, Fernstrom JD, Fernstrom MH et al.
Gastric bypass surgery for morbid obesity leads to an
increase in bone turnover and a decrease in bone
mass. J Clin Endocrinol Metab 2004; 89: 1061-5.
27.Compston JE, Vedi S, Ledger JE et al. Vitamin D status and bone histomorphometry in gross obesity. Am
J Clin Nutr 1981; 34: 2359-63.
28.Hamoui N, Anthone G, Crookes PF. Calcium metabolism in the morbidly obese. Obes Surg 2004; 14: 912.
29.Parikh SJ, Edelman M, Uwaifo GI et al. The relationship between obesity and serum 1,25 dihydroxy vitamin D concentrations in healthy adults. J Clin
Endocrinol Metab 2004; 89: 1196-9.
(Received May 13, 2004; accepted July 14, 2004)