ORIGINAL PAPER

Bariatric Surgery and Effects on Calcium and Bone Metabolism

Khashayar Sakhaee

� Springer Science+Business Media New York 2013

Abstract With the increasing epidemic of obesity in the

United States as well as abroad, bariatric surgery has

emerged as the most effective and sustained treatment for

reduction. This treatment modality has been well recog-

nized to diminish the risk of cardiovascular morbidity and

mortality and ameliorate diabetes mellitus. However, with

time, derangement in mineral metabolism has emerged as a

major complication in this population. Population-based

study has shown increased prevalence of bone fractures and

kidney stone formation following bariatric surgery. The risk

appears to be more specific after Roux-en-Y gastric bypass

procedures, the most common surgical approach among this

population. Over the past decade, there have been advances

in the understanding of pathophysiologic mechanisms of

both bone loss and kidney stone disease in these patients.

The understanding of these underlying pathophysiologic

mechanisms may lead to the development of drug therapies

that ameliorate this complication. Unfortunately, at the

present time, there is no hard data on any specific treatment

showing decreased incidence of fragility fractures or kidney

stone passage. However, some studies suggest that calcium

and vitamin D supplementation may decrease bone loss and

bone turnover, and as a result, increase bone mineral density

in this population. However, there is concern with the

development of kidney stone formation following such an

approach. A novel treatment approach would be the use of

effervescent potassium calcium citrate that not only pre-

vents complications of bone loss but may diminish the risk

of kidney stone formation. Despite preliminary results

showing the effectiveness of this drug in the reduction in the

parathyroid hormone, bone turnover, and improvement in

the urinary saturation marker showing effectiveness against

calcium oxalate and uric acid stones, there is no hard data

available to support the effectiveness of this treatment in the

reduction in fragility fractures or kidney stone incidence.

Such studies to explore this effect must be considered in the

future.

Keywords Bariatric surgery � Roux-en-Y � Kidney

stones � Bone loss

Introduction

Bariatric surgery has been shown to induce sustained

weight loss, thereby significantly reducing morbidity and

mortality related to obesity [1–3]. With the epidemic of

overweight and obese populations [4], there has been

growing interest in medical and surgical management of

obesity. Lifestyle modification and medical therapy induce

short-term weight loss with difficult long-term mainte-

nance [5, 6]. As a result, an increasing number of surgical

operations have been performed in the United States [2, 5,

7]. Previous surgical operations, such as Jejunoileal bypass

and biliopancreatic diversions (BPD), have been either

abandoned or diminished due to severe morbidity and

mortality [8–11].

In recent years, Roux-en-Y gastric bypass (RYGB) and

gastric banding have been promoted [12]. Although these

procedures have been successful and salutary in reducing

the complications of obesity [6, 13, 14], skeletal bone

disease [15–20] and nephrolithiasis [21–26] have emerged

as the main complications of RYGB.

K. Sakhaee (&)

Department of Internal Medicine, University of Texas

Southwestern Medical Center at Dallas, 5323 Harry Hines

Boulevard, Dallas, TX 75390-8885, USA

e-mail: khashayar.sakhaee@utsouthwestern.edu

123

Clinic Rev Bone Miner Metab

DOI 10.1007/s12018-013-9145-2

Prevalence of Bone Fracture and Changes in Bone

Mineral Density Following Bariatric Surgery

Bone Changes Post-RYGB

Despite the abundance of studies addressing the patho-

physiologic mechanisms and changes in bone turnover and

bone density, there is paucity of the data addressing the

incidence of skeletal fractures 2–4 years after bariatric

surgery. In one retrospective study, a telephone survey was

obtained in 167 subjects, 12–16 months after RYGB for

morbid obesity, to evaluate the incidence of fracture [27].

The mean age of the studied subjects was 47 years with

women comprising 80 % of the participants. Six percent of

the subjects self-reported a decrease in height and 5 %

admitted appendicular skeletal fractures. Moreover, one

significant finding of the study was the high incidence of

repeated falls following surgery.

Several prospective studies have demonstrated changes

in bone mineral density (BMD) and bone turnover fol-

lowing various bariatric procedures. One prospective study

of 42 obese women (mean 37.7 years of age) 12 months

post-RYGB procedures showed a significant reduction in

the lumbar BMD and total femoral BMD of 7.4 and

10.5 %, respectively, despite calcium intake of

640–1,000 mg and vitamin D of 400–800 U/day [28].

Another study compared bone mineral density to calci-

tropic hormone in 11 non-obese, 12 obese, and 16 obese

3 years following RYGB surgery. In only subjects fol-

lowing RYGB, a significant reduction in BMD was found

at all skeletal sites. However, serum parathyroid (PTH) and

25-hydroxyvitamin D (25-OHD) levels remained unchan-

ged among all three groups while urinary deoxypyridino-

line (DPD) increased only in those following RYGB [29].

In a 1-year prospective study of 223 males and females

1 year following RYGB, ranging 21–64 years of age,

despite adequate calcium and vitamin D supplementation,

there was a significant reduction in the BMD at the femoral

neck of 9.2 %. The decrease in BMD at this site was

strongly associated with the degree of weight loss and

serum PTH. Moreover, urinary N-telopeptide (NTX)

increased significantly 3 months after surgery and

remained elevated at 12 months [17].

Four other studies collectively including 124 subjects

following RYGB showed significant fall in BMD at the

lumbar spine and hip [18, 30–32]. A very recent study of

14 women 1 year post-RYGB found that BMD did not

change at the spine or forearm, but fell significantly at the

femoral neck and total hip by 4.5 and 5.2 %, respectively.

These losses occurred despite adequate supplementation

with vitamin D and calcium [20]. This study, using high-

resolution peripheral quantitative computed tomography

(HR-pOCT), showed preferential fall in the cortical area,

cortical thickness, and total area. The changes in cortical

bone parameters were highly associated with a rise in PTH

levels. The result of this study supports that RYGB in

particular affects bone loss specifically at weight-bearing

sites including the femoral neck and total hip [17–19, 28]

(Table 1).

Bone Changes Post-gastric Banding

and Biliopancreatic Diversions

A limited number of studies have addressed the changes in

BMD, calcitropic hormones, and bone turnover markers

following gastric banding procedures and BPD. In one

study of 16 morbidly obese subjects who underwent ver-

tical banded gastroplasty (VGB), BMD, bone turnover and

calcitropic hormones were assessed 12 months after sur-

gery [33]. The results showed that BMD at the femoral

neck, trochanter, and Ward’s triangle decreased signifi-

cantly. These changes were associated with significant

increases in urinary DPD, suggestive of increased bone

turnover; however, no significant change was detected in

serum PTH. In another study, 18 patients were observed

before and after VGB. Two years following the surgery,

there was no change in BMD at the spine, but a significant

fall in BMD at the trochanter and Ward’s triangle was

noted. These changes were associated with the increased

bone resorption marker DPD; however, there was no

change in serum PTH or 25-OHD [34].

One study followed 33 subjects who underwent BPD for

10 years [35]. The results of this study showed no change

in BMD at the hip, but noted significant decrease in BMD

at the lumbar spine despite adequate supplementation with

calcium and vitamin D. These changes were associated

with a significant fall in serum 25-OHD and increases in

serum PTH, bone-specific alkaline phosphatase, and oste-

ocalcin. In another study of 63 patients undergoing BPD,

increased PTH and osteocalcin (a marker of bone turnover)

and C-terminal telopeptide of type I collagen (CTX) were

associated with decreased BMD at the spine, but not at the

hip. In another study, 96 morbidly obese patients following

BPD demonstrated an increased reduction in the bone

resorption marker, DPD, and serum PTH 2 years after the

surgery [36]. However, in this instance, BMD was not

assessed.

Pathophysiologic Mechanisms of Bone Loss Following

Bariatric Surgery

Pathophysiologic mechanisms of bone loss after bariatric

surgery are complex and may include alterations in

Clinic Rev Bone Miner Metab

123

mechanical effects on bone, nutritional deficiencies,

abnormalities in calcitropic hormone metabolism, and

alterations in energy metabolism with modulation in adi-

pokines and intestinal hormones affected following bari-

atric surgery (Fig. 1). The PubMed Review using key

words ‘‘bariatric surgery, weight loss, bone loss, and bone

metabolism’’ until 2006 has shown that bone loss fre-

quently occurs after bariatric surgery, more specifically

after RYGB procedures.

Role of Mechanical Unloading on a Skeleton

Under normal physiological circumstances, mechanical

loading has been shown to play a major role in attaining

bone mass, bone strength, and bone size [37, 38]. In

addition to bariatric surgery, several clinical conditions

associated with immobility and unloading of the skeleton

have been reported to be associated with weight loss [39–

42]. Bariatric surgery in particular has been associated with

bone loss at weight-bearing skeletal sites including the total

hip and femoral neck [17–19, 28].

The molecular mechanism of skeletal unloading has

been attributed to the up-regulation of mRNA for the

sclerostin gene (SOST). A study in SOST-deficient mice

shows that sclerostin plays an important role following

unloading the skeleton [43]. Mechanical unloading has

been demonstrated to reduce osteoblastic bone function

and consequently diminish bone formation. In this popu-

lation, increased sclerostin production through negative

regulation of WnT signaling influences osteoblastic cell

differentiation and function [44].

Role of Nutritional Deficiencies on a Skeleton

Generally, obese individuals may suffer from 25-OHD

deficiency prior to bariatric surgery [45]. The perturbation

of vitamin D metabolism may be physiological due to the

redistribution of vitamin D into the fat tissue and in part

may be acquired by way of lifestyle including insufficient

exposure to sun and social limitations [46–49]. Further-

more, in malabsorptive surgeries including RYGB, mal-

absorption of nutrients such as minerals and vitamin D due

to the loss of intestinal surface area is common [19, 28].

Therefore, as a consequence of these nutritional deficien-

cies, secondary parathyroid hormone (PTH) stimulation

will ensue and stimulate bone loss [17, 31, 50].

Restrictive bariatric surgery with the limitation of food

intake may also have adverse effects on the skeleton. The

changes in skeletal homeostasis in this population may be

associated without alteration in serum calcium and calci-

tropic hormones [34, 51].

Table 1 Bone mineral density changes following bariatric surgery

Author Number of

patients

Mean

BMI

Type of

surgery

Duration of

study (months)

Supplements Outcome BMD

Carrasco 42 45 RYGB 12 Calcium (640–1,000 mg/day)

Vitamin D (400–800 U/day)

Spine (-7.4 %)*

Total hip (-10.5 %)*

Pereira 16 33 RYGB 12 Calcium (250 mg/day)

Vitamin D (400 U/day)

Spine (-6.2 %)*

Forearm (-5.1 %)*

Femoral neck (-10.2 %)*

Fleischer 23 47 RYGB 12 Calcium (1,318 mg/day)

Vitamin D (658 U/day)

Femoral neck (-9.2 %)*

Coates 25 31 RYGB 11 Calcium (1,200 mg/day)

Vitamin D (400–800 U/day)

Spine (-3.3 %)*

Femoral neck (-5.1 %)*

Total hip (-7.8 %)*

Johnson 226 50 RYGB 36 Calcium (1,200 mg/day)

3 multivitamins

Spine (-4.5 %)*

Radius (-1.8 %)*

Total hip (-9.2 %)*

Stein 14 44 RYGB 12 Calcium (1,500–1,800 mg/day)

Vitamin D (400–800 U/day)

Femoral neck (-4.5 %)*

Total hip (-5.2 %)*

Cundy 18 43 VGB 24 Calcifediol (75 mcg/day) Ward’s triangle (-3.9 %)*

Trochanter (-4.8 %)*

Guney 16 46 VGB 12 None Femoral neck (-4.8 %)*

RYGB Roux-en-Y gastric bypass, VGB vertical banded gastroplasty

* Significant reduction in bone mineral density (BMD)

Clinic Rev Bone Miner Metab

123

Fig. 1 Pathophysiologic

mechanisms of bone loss and

kidney stone formation

following bariatric surgery

Clinic Rev Bone Miner Metab

123

Role of Calcitropic Hormone Metabolism

Abnormalities on a Skeleton

A large body of data supports the development of sec-

ondary PTH in the pathogenesis of bone loss after RYGB

and biliopancreatic diversions [31, 52, 53]. The principal

cause of bone loss after RYGB procedures has been

attributed to defective calcium absorption associated with

secondary PTH stimulation from lowered intestinal cal-

cium absorption [54, 55]. The impaired intestinal calcium

absorption has been attributed to limiting the exposure of

nutrients, which impairs the solubility of calcium salt and

fast intestinal transit [52, 53].

Vitamin D deficiency has been reported following both

malabsorptive and restrictive bariatric surgeries. Several

studies have reported low serum 25-OHD following gastric

surgery, thereby showing that vitamin D malabsorption and

secondary PTH stimulation persist despite restoration of

the calcium and vitamin D intake [16, 17, 56–58]. A ret-

rospective study showed a 73 % incidence of vitamin D

deficiency following biliopancreatic diversion procedures

[59]. Furthermore, in a study with patients following sleeve

gastrectomy, vitamin D deficiency was found in 39 % of

the subjects after 1 year despite daily multivitamin sup-

plementation [60]. Regardless of the type of bariatric sur-

gery, the prevalence of secondary PTH, increased bone

turnover, and bone mineral density loss were high in all

these populations [17, 52, 61].

Role of Energy Metabolism Alterations on a Skeleton:

Leptin

Recent advances in neurohormonal regulation of bone

metabolism have opened the door to define the significant

role of adipokines in the regulation of bone metabolism

after bariatric surgery [62]. Our knowledge of the role of

adipokines in human bone disease has not yet been fully

explored. However, leptin, which is released by adipocytes,

and its level have been shown to be significantly lower in

subjects following gastric bypass surgery compared to

obese controls [18, 63]. Nevertheless, its association with

bone mineral density has not been shown to be strong,

reflecting its dual role on bone remodeling [64]. The effect

of leptin on bone remodeling is exerted through two

independent central nervous system pathways. One mech-

anism involves the activation of sympathetic nervous sys-

tem and the stimulation of bone formation [65, 66]. The

second pathway is through the activation of cocaine–

amphetamine-regulated transcript (CART), which in turn

leads to the stimulation of receptor activator of nuclear

factor-kappa B ligand (RANK-L) expression in osteoblast,

which finally leads to enhanced bone resorption [67].

Following bariatric surgery, a fall of leptin levels is

associated with an imbalance in bone turnover, with bone

resorption exceeding bone formation thereby resulting in

net bone loss [63, 68].

Role of Energy Metabolism Alterations on a Skeleton:

Adiponectin

Adiponectin originates from adipocytes, and it has been

shown that its level is significantly increased after gastric

bypass surgery [28]. Its level has been shown to be

inversely related to the fall of bone mineral density fol-

lowing gastric bypass surgery. Its invitro effect has been

shown to be through the stimulation of RANK-L and

inhibits osteoprotegerin (OPG) in human osteoblasts [69].

Role of Energy Metabolism Alterations on a Skeleton:

Peptides

Ghrelin is a peptide produced by the stomach, which

stimulates hunger in humans [70]. Ghrelin levels diminish

following RYGB and gastric sleeve procedures. Thus, it

appears that stomach fundus plays a key role in the

secretion of this peptide [71]. The effect of the changes in

ghrelin on bone metabolism has not yet been explored in

human subjects. However, it has been shown that ghrelin

increases perforation and differentiation of osteoblasts

[72].

Peptide YY (PYY) is in the polypeptide family that

includes neuropeptide Y and pancreatic polypeptides. It is

produced by the small intestinal and colonic L cells

postprandially [70]. Following RYGB, biliopancreatic

diversions, and adjustable gastric banding, its level

increases [73–75]. At the present time, no clinical study has

shown a relationship between this peptide and bone density

in human subjects following bariatric surgery.

Glucagon-like peptides (GLP-1 and GLP-2) are also

secreted postprandially by intestinal L cells [76]. Their

levels increase significantly following RYGB procedures.

Its effect on bone turnover and bone density has not yet

been fully demonstrated; however, administering GLP-1

has been shown to improve bone density [77].

Role of Energy Metabolism Alterations on a Skeleton:

Sex Hormones

Adipocytes are the site of conversion of testosterone to

estradiol under the influence of aromatase [78]. There is

scanty literature with regard to changes in estrogen levels

following bariatric surgery. However, it has been shown

that estrogen levels generally decrease with weight loss in

both genders. Thereby, a fall in estrogen levels may either

directly or indirectly affect bone metabolism through

alteration in calcitropic hormone metabolism [79, 80].

Clinic Rev Bone Miner Metab

123

Prevalence of Kidney Stone Formation Following

Bariatric Surgery

Kidney stones have emerged as one of the main compli-

cations of modern bariatric surgeries. There are a limited

number of population-based studies concerning the preva-

lence of kidney stones following bariatric surgery. Using a

database from a national private insurance claim, one study

compared 4,690 patients who underwent RYGB with a

control group of obese subjects. It was shown that 7.5 % of

RYGB patients were diagnosed with kidney stones com-

pared with only 4.63 % of obese control patients [21].

Another retrospective study of 972 patients who underwent

RYGB found that 8.8 % admitted to kidney stones prior to

surgery and 3.2 % developed new stones postoperatively.

Of the known kidney stone formers in this population,

31 % had recurrent kidney stones following surgery.

Therefore, the stone prevalence was reported to be

approximately 70 % in the bariatric surgery population

[81].

Gastric banding was shown not to be associated with

kidney stone formation utilizing a national private insur-

ance claims database between 2002 and 2006. After gastric

banding, 1.49 % of subjects formed stones compared to

5.97 % in obese controls [82].

Pathophysiologic Mechanisms of Kidney Stone

Formation Following Bariatric Surgery

Kidney Stone Formation Following RYGB Surgery

Pathophysiologic mechanisms for kidney stone develop-

ment following RYGB surgery are numerous and include

low urine volume, high urinary oxalate, low urinary pH,

and low urinary citrate [22–26, 83–85] (Table 2).

Role of Low Urine Volume

Low urine volume is commonly encountered after RYGB

surgery as a result of low fluid intake due to a restricted

reservoir [25, 26, 83].

Role of High Urinary Oxalate

Hyperoxaluria is the most common risk factor in the

development of kidney stones in patients following RYBG

surgery. In fact, it has been detected in one- to two-thirds of

patients in this population [22–26, 83–85]. This abnor-

mality may occur early or late depending on the type of

surgery, health of the patient, and differences in dietary

intake of protein, fat, calcium, and oxalate [26, 83, 85].

Despite the common belief that RYGB surgery overcame

the complication of kidney stone formation previously

caused by Jegunoileal (JI) [86], a 2005 study showed an

association between RYGB and kidney stone formation

[22]. In this study, 21 out of 23 patients who underwent

RYGB developed kidney stones associated with highly

Table 2 Kidney stone risk profiles following RYGB surgery

Before RYGB Following RYGB

Urinary oxalate

Nelson et al. [22] N/A 79

Sinha et al. [23] 31 ± 16 65 ± 39*

Asplin and Coe [24] N/A 85 ± 44*

Duffey et al. [26] 31 ± 10 41 ± 18*

Penniston et al. [97] N/A 48 ± 4

Park et al. [25] 32 (median) 40 (median)*

Maalouf et al. [93] N/A 45 ± 21*

Patel et al. [84] N/A 61 ± 4*

Kumar et al. [85] 26 ± 13 32 ± 11 (NS)

Froeder et al. [94] N/A 26 (median)(NS)

Urinary Citrate (mg/day)

Sinha et al. [23] 660 ± 297 444 ± 376(NS)

Asplin and Coe [24] N/A 477 ± 330*

Penniston et al. [97] N/A 441 ± 71*

Park et al. [25] 675 (median) 456 (median)*

Maalouf et al. [93] N/A 358 ± 357*

Patel et al. [84] N/A 621 ± 40*

Froeder et al. [94] N/A 472 (median)(NS)

Urinary pH

Asplin and Coe [24] N/A 5.72 ± 0.31*

Sinha et al. [23] 5.96 ± 0.38 5.78 ± 0.59(NS)

Duffey et al. [26] 5.82 ± 0.54 5.66 ± 0.43(NS)

Park et al. [25] 6.03 (median) 5.75 (median) (NS)

Froeder et al. [94] N/A 5.78 (median) (NS)

Urinary volume (mg/day)

Duffey et al. [26] 1,380 ± 400 900 ± 430*

Park et al. [25] 1,800 (median) 1,440*

Maalouf et al. [93] N/A 1,900 ± 900 (NS)

Kumar et al. [85] 2,091 ± 768 1,316 ± 540*

Froeder et al. [94] N/A 1,140*

Urinary calcium (mg/day)

Sinha et al. [23] 206 ± 111 112 ± 92*

Asplin and Coe [24] N/A 141 ± 61*

Duffey et al. [26] 206 ± 111 112 ± 92*

Fleischer et al. [17] 161 ± 22 92 ± 15*

Penniston et al. [97] N/A 100 ± 12*

Park et al. [25] 176 (median) 135* (median)

Maalouf et al. [93] N/A 115 ± 93*

Froeder et al. [94] N/A 89* (median)

N/A not available, NS statistically nonsignificant

* Significant compared to control

Clinic Rev Bone Miner Metab

123

elevated urinary oxalate. Moreover, 2 patients developed

acute renal injury due to high oxalate burden in the kidney.

Following that report, several investigators reported high

incidence of kidney stone, hyperoxaluria, and elevated

urinary supersaturation with respect to calcium oxalate [23,

24, 84, 85] (Fig. 1).

The underlying pathophysiologic mechanisms for

hyperoxaluria following RYGB procedure have not yet

been fully elucidated. (1) One purported mechanism has

linked hyperoxaluria to intestinal fat malabsorption [85,

87]. In this scheme, the unabsorbed fat increases free

luminal oxalate content by binding to calcium in intestinal

lumen and thereby enhancing intestinal oxalate absorption.

However, few studies have alluded to fecal fat excretion in

this population [85, 88]. (2) Moreover, it has been sug-

gested that changes in intestinal microbial flora following

bariatric surgery can potentially modify the colonization of

lower intestinal flora with respect to oxalobacter formig-

enes, which is recognized for its capacity to degrade oxa-

late [89, 90]. However, this pathogenetic scheme has not

yet been well elucidated among the population. (3) Yet,

another mechanism has been suggested to be due to

increased permeability of the colon as a result of exposure

to unconjugated bile acids and long-chain fatty acids fol-

lowing RYGB procedures [91, 92].

Role of Low Urinary pH

In two studies, low urinary pH has been shown following

RYGB procedure [25, 93], associated with supersaturation

of uric acid.

Role of Low Urinary Citrate

Low urinary citrate is found in the majority of, but not all,

patients following RYGB [23, 24, 26, 84, 85]. However, its

prevalence has been demonstrated to vary with different

reports ranging between 34 and 63 % [25, 83, 93, 94].

Hypocitraturia occurs in this population in the absence of

overt metabolic acidosis, suggesting the homeostatic role

of the skeleton in the buffering of an excessive acid load

[95].

Kidney Stone Formation Following Restrictive Surgery

Two studies explore the biochemical profile following

gastric banding and/or sleeve gastrectomy. In one study, a

total of 18 patients (14 with gastric banding and 4 with stiff

gastrectomy) were studied for 6 months following surgery.

The urinary kidney stone risk profiles were compared with

the RYGB cohort [96]. In this study, urinary oxalate

excretion and urinary supersaturation calcium oxalate were

comparable to control subjects, but significantly lower in

restrictive cohorts (gastric banding and sleeve gastrectomy)

compared with the RYGB population. Similar findings

were obtained in another cohort comparing 21 subjects

who underwent RYGB and 12 who underwent gastric

banding. The results showed that patients with gastric

banding had low urinary volume, but did not have other

kidney stone risk factors that were detected in the cohort

who underwent RYGB, including hypocitraturia and

hyperoxaluria [97].

Role of Urinary Calcium

Low urinary calcium is commonly encountered following

RYGB procedures, which plays an inhibitory role against

calcium oxalate crystallization by overriding the effect of

hypocitraturia and hyperoxaluria [17, 23, 25, 26, 93, 97].

The underlying mechanism of hypocalciuria is associated

with impaired intestinal calcium absorption [54, 98].

Potential Treatment Approach Toward Skeletal Bone

Disease and Kidney Stone Formation Following

Bariatric Surgery

Despite the availability of hard evidence of bone fracture

efficacy data, the American Association of Clinical Endo-

crinologists (AACE), the Obesity Society (TOS), and the

American Society of Metabolic and Bariatric Surgery

(ASMBS) have recommended that calcium supplementa-

tion be considered after bariatric surgery [99]. These

guidelines advocate the daily treatment 1,200–2,000 mg of

calcium and ergocalciferol at 50,000 U 1–2 times/week

and higher doses up to 50,000–150,000 U/day for severe

vitamin D deficiency. In rare instances when the subject

does not respond to the maximal does of ergocalciferol,

calcitriol treatment may be the drug of choice.

The above recommendation is pathophysiologically

logical since impaired intestinal calcium absorption occurs

[54, 98] associated with vitamin D deficiency and sec-

ondary parathyroid stimulation, which commonly befalls

this population [17, 19, 28, 31, 50]. In addition, GI alkali

loss occurs following RYGB surgery increasing the risk of

kidney stone complication [22, 23, 93].

AACE/TOS/ASMBS guidelines recommend calcium

citrate tablets as the preferred choice in this population due

to its superior intestinal bioavailability [100, 101]. The low

intestinal bioavailability of calcium carbonate was shown

to be due to diminished solubility as a result of the lack of

exposure of duodenum, the main site of calcium absorp-

tion, to gastric acid secretion and also due to rapid intes-

tinal transit time [102]. However, the latter was based on

the study in postmenopausal women comparing the tablet

formulation of calcium carbonate and calcium citrate.

Clinic Rev Bone Miner Metab

123

Since then, it was found that calcium citrate in tablet for-

mulation is not efficiently absorbed in the RYGB popula-

tion [98, 103]. Moreover, both calcium citrate and calcium

carbonate in tablet forms were not shown to ameliorate

PTH secretion in RYGB patients [98, 100, 103].

It is imperative to use a product to overcome the above

limitations of calcium citrate tablets and reverse the path-

ophysiologic derangements responsible for the develop-

ment of bone loss and kidney stone formation. Recently, in

a short-term, randomized, crossover placebo control trial

study in 24 patients following RYGB, it was shown that

effervescent potassium calcium citrate (PCC) significantly

inhibited bone turnover by lowering PTH secretion [104]

(Fig. 2a, b). Moreover, alkali provision from PCC

increased urinary pH and citrate, while attenuating a rise in

urinary calcium from increased intestinal calcium absorp-

tion. The aforementioned changes were associated with an

increased inhibition against calcium oxalate agglomera-

tions and reducing urinary supersaturation of uric acid

(Fig. 3a, b). Despite the availability of hard evidence such

as bone fracture efficacy and kidney stone incidence, this

novel approach appears promising and requires further

investigation.

Although bisphosphonates are the drug of choice in the

management of senile osteoporosis, there is concern with

the use of this drug in the RYGB population. This stems

from case reports suggesting that underlying intestinal

calcium and vitamin D malabsorption may accentuate the

development of severe hypocalcemia after the administra-

tion of bisphosphonate in this population [105].

Conclusion

The benefits of bariatric surgery in sustaining weight loss

and its increased benefit in the reduction in cardiovascular

and diabetic complications have been well established.

However, metabolic complications including bone loss and

nephrolithiasis are almost inevitable. It has been shown that

RYGB is the most effective among all procedures. How-

ever, it carries the highest metabolic risk. Therefore, it is

imperative that patients receive prophylactic measures to

avoid this complication. To date, the use of commonly

prescribed over-the-counter calcium supplement and vita-

min D supplementation has not been shown to avert bone

loss. This limitation has been to a major extent due to

significantly impaired intestinal calcium absorption.

Despite treatment with calcium supplements in tablet

Fig. 2 [104]: a Effect of PCC and placebo on serum calcium (Ca)

and PTH. Vertical bars indicate mean ± SD. Dashed horizontal line

represents upper normal limit of serum PTH. b Effect of PCC and

placebo on serum CTX and urinary deoxypyridinoline (DPD). Dashed

horizontal lines represent upper normal limits. **P \ .01; �P \ .001

between 2 phasesFig. 3 [104]: a Effect of PCC and placebo on Supersaturation Index

(SI) of calcium oxalate (Ca oxalate), brushite, and uric acid. Dashed

horizontal line indicates saturation value. b Effect of PCC and

placebo on agglomeration inhibition of calcium oxalate. Data

individually depicted for 8 urine samples, in which concentrations

of citrate, calcium, and pH were altered to mimic those of PCC and

placebo phases

Clinic Rev Bone Miner Metab

123

formulation, it appears that a pre-solubilized calcium cit-

rate and potassium citrate formulation will overcome these

limitations and reverse underlying pathophysiologic

abnormalities responsible for the development of both bone

loss and kidney stone formation. A preliminary study has

suggested an improvement in bone turnover and reduction

in kidney stone risk in this population. However, despite

this evidence, there is a lack of hard data showing the

effectiveness of this formulation in the reduction in fracture

and kidney stone incidence. Future investigation is needed

to explore these effects.

Acknowledgments The author would like to acknowledge Ashlei

L. Johnson for her role in the editorial process of this manuscript.

Disclosures

Conflict of interest Khashayar Sakhaee declares that he has no

conflict of interest.

Animal/Human Studies This article does not contain any studies

with human or animal subjects performed by the author.

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