INTRODUCTION — Osteoporosis is common in patients with inflammatory bowel diseases (IBD) such as Crohn disease (CD) or ulcerative colitis (UC). In cross-sectional studies of patients with IBD, the prevalence of osteoporosis ranges from 18 to 42 percent [1,2]. In patients newly diagnosed with IBD, the prevalence is much lower (0 to 5 percent) [1].
The etiology of low bone mass is multifactorial and includes corticosteroid therapy, disease-related inflammatory activity, dietary restrictions, malabsorption, and hypogonadism [3,4].
This topic review will focus on the risk factors for and the evaluation and treatment of bone disease in patients with IBD. The diagnosis and treatment of osteoporosis in pre- and postmenopausal women and men and the prevention and treatment of glucocorticoid-induced osteoporosis are reviewed elsewhere. (See "Evaluation and treatment of premenopausal osteoporosis" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women" and "Overview of the management of osteoporosis in postmenopausal women" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men" and "Treatment of osteoporosis in men" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)
SKELETAL OUTCOMES
Bone mineral density — In cross-sectional studies, osteoporosis (T-score <-2.5) has been noted in approximately 18 to 42 percent of patients with established IBD [1,2]. The prevalence of osteopenia (T-score between -1 and -2.5) ranges from 22 to 77 percent [4]. In a meta-analysis of 16 studies of bone mineral density (BMD) in IBD compared with controls, the mean Z-scores at all sites were lower in patients with IBD (mean difference ranging from -0.5 to -1) [5]. In some [6-9], but not all [10-15], studies, low bone mass is more common in patients with Crohn disease (CD) than ulcerative colitis (UC).
Fracture — In some [16-18], but not all [19], population-based studies, there was an increased risk of fracture in individuals with IBD. In the largest study (6027 patients with IBD), the overall fracture rate was higher than that for controls (relative risk [RR] 1.4, 95% CI 1.3-1.6) [16]. The increased risk occurred primarily in older (>60 years) patients. There was no difference between UC and CD. In a meta-analysis of studies that evaluated specific types of fractures in patients with IBD, there was an increase in risk of vertebral fracture (1.34 versus 0.56 percent in healthy controls, odds ratio [OR] 2.26, 95% CI 1.04-4.90) [5]. The increase in risk of hip fracture was not significant (2.4 versus 1.7 percent, OR 1.29, 95% CI 0.84-1.96). In one of the studies, risk of fracture increased with duration of corticosteroid use [20]. Although low BMD is a risk for fracture, many individuals have normal BMD at the time of fracture diagnosis [21].
RISK FACTORS — Patients with IBD are at risk for osteoporosis and fracture for several reasons, including disease-related inflammatory activity, corticosteroid therapy, hypogonadism, and nutritional deficiencies [4,22]. Advanced age and low body mass index (BMI) further increase risk [23,24].
Disease-related inflammatory activity — Some patients with IBD have low bone mineral density (BMD) in the absence of other identifiable risk factors. This can be illustrated by the following observations:
●Some patients with Crohn disease (CD) have a low BMD at the time of diagnosis, before any treatment is given [7].
●Osteoporosis is common in patients with IBD who have received little corticosteroid and who are vitamin D replete [12].
The cause of low BMD in these untreated patients is not understood. In some cases, bone resorption is increased without a compensatory increase in bone formation. One possibility is that the chronic inflammatory state leads to increased intestinal production of cytokines (eg, interleukins 1 and 6, tumor necrosis factor [TNF]) that stimulate bone resorption [1,4,22,25]. In support of this hypothesis is the finding that maintenance treatment with the anti-TNF, infliximab, was associated with improvement in BMD in patients with CD, implicating a role for TNF-alpha in bone loss. (See "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease" and "Overview of medical management of high-risk, adult patients with moderate to severe Crohn disease".)
Changes in the RANKL (receptor activator of NF-kappa B ligand)/OPG (osteoprotegerin) system may also contribute to low bone mass in patients with IBD [26,27]. RANKL is expressed by cells of the osteoblast lineage. It interacts with a receptor on osteoclast precursors called RANK. The RANKL/RANK interaction results in activation of cells in the osteoclast lineage to begin the process of osteoclastogenesis and bone resorption. However, RANKL can also bind to a soluble decoy receptor called OPG. OPG blocks the interaction of RANKL and RANK, thereby preventing osteoclast activation and bone resorption. (See "Normal skeletal development and regulation of bone formation and resorption", section on 'Osteoclasts'.)
In one study of patients with IBD, plasma OPG and RANKL were elevated and correlated with BMD [27]. Further studies are required to assess the role of the RANKL/RANK/OPG system in bone loss in patients with IBD. If RANKL is shown to play an important role, denosumab, a monoclonal antibody to RANKL, may prove to be an effective therapy for osteoporosis in IBD. (See "Denosumab for osteoporosis", section on 'Mechanism of action'.)
Glucocorticoid therapy — Many patients with IBD receive glucocorticoids to reduce intestinal inflammation. Glucocorticoids cause bone loss by inhibiting bone formation, increasing bone resorption, decreasing intestinal absorption of calcium, and increasing renal excretion of calcium. (See "Clinical features and evaluation of glucocorticoid-induced osteoporosis".)
Bone loss is more common in patients with IBD who have been treated with glucocorticoids [8]. In one report, for example, the incidence of osteopenia was approximately twice as high (52 versus 28 percent) in patients who had been treated with corticosteroids compared with those who had not [11]. In general, BMD in patients with IBD is inversely correlated with lifetime corticosteroids dose [3,6,10,11,13,28]. However, it is difficult to distinguish the adverse skeletal effects of corticosteroids from those of disease-related inflammatory activity because the two factors are often linked [1].
Alterations in sex hormone status — Hypogonadism is common in both men and women with IBD, probably because of the inhibitory effects of the illness and corticosteroid therapy on pituitary-gonadal function [29]. In men, corticosteroid therapy lowers serum testosterone concentrations by approximately one-third, primarily by inhibiting gonadotropin secretion [30]. Gonadal steroid deficiency is a well-recognized cause of osteoporosis in both men and women. (See "Etiology of osteoporosis in men" and "Epidemiology and etiology of premenopausal osteoporosis".)
Vitamin D and calcium insufficiency — Vitamin D insufficiency is common in patients with IBD. In one study, 65 percent of patients with CD had low serum calcidiol (25-hydroxyvitamin D) concentrations [31]. This problem is in part due to malabsorption, particularly in patients with CD who have a history of small bowel resection (figure 1) [32]. Avoidance of dairy products may also contribute to vitamin D insufficiency. One study, for example, found that dietary calcium intake below 1000 mg/day was more common in patients with CD than in normal subjects (53 versus 27 percent) [28].
However, BMD is reduced even in many patients who are vitamin D replete [11,12]. Thus, vitamin D deficiency is not the main cause of osteoporosis in most patients with IBD.
Other nutritional deficiencies — Macronutrient (protein, overall calories) and micronutrient (vitamins and minerals) deficiencies are common in patients with IBD, including patients maintained on parenteral nutrition [33], and may contribute to bone disease. (See "Vitamin and mineral deficiencies in inflammatory bowel disease".)
EVALUATION
Assessment of clinical risk for fracture — The goal of the clinical evaluation is to identify patients with IBD who are at high risk for bone loss and fracture. Many studies have demonstrated that low bone mineral density (BMD) is associated with an increased risk of fracture. However, there are several clinical risk factors for fracture that are independent of BMD, such as advancing age, prior history of fragility fracture, chronic corticosteroid use, low body mass index (BMI), parental history of hip fracture, cigarette smoking, and excess alcohol. Thus, fracture risk assessment should include evaluation of the following:
●Clinical risk factors for osteoporosis
●BMD measured by dual-energy x-ray absorptiometry (DXA)
We typically perform a history and physical examination to elicit clinical risk factors for fracture and lifestyle factors that contribute to bone loss, including smoking, excessive alcohol, physical inactivity, and poor nutrition (table 1).
We obtain a BMD study (DXA spine and hip) in patients with IBD who are at higher risk for osteoporosis and fracture (previous fragility fracture, postmenopausal, male >50 years, hypogonadism, or chronic [>3 months] glucocorticoid therapy). This is largely in agreement with the American Gastroenterological Association (AGA) and British Society of Gastroenterologists guidelines [1,34,35].
Osteoporosis risk factor assessment is reviewed in greater detail separately. (See "Osteoporotic fracture risk assessment", section on 'Dual-energy x-ray absorptiometry (DXA)' and "Osteoporotic fracture risk assessment", section on 'Skeletal site to measure' and "Osteoporotic fracture risk assessment", section on 'Clinical risk factor assessment'.)
Interpretation of DXA — The World Health Organization (WHO) has established a classification of BMD according to dual-energy x-ray absorptiometry (DXA) T-score that is the worldwide standard for diagnosis of osteoporosis in postmenopausal women and men >50 years of age (table 2). However, in premenopausal women, men <50 years of age, and children, the relationship between BMD and fracture risk is not well established. In these groups, Z-scores, not T-scores, should be used to interpret DXA scans. In addition, a diagnosis of osteoporosis in younger men, premenopausal women, and children should not be based upon DXA results alone. (See "Overview of dual-energy x-ray absorptiometry", section on 'Diagnosis of osteoporosis' and "Epidemiology and etiology of premenopausal osteoporosis", section on 'Definitions'.)
The DXA criteria used to make therapeutic decisions are discussed below. (See 'Candidates for therapy' below.)
BMD monitoring — While there are a number of approaches to monitoring bone mineral density (BMD), there is no consensus on the optimal approach. For patients with normal initial BMD results, the AGA recommends repeat testing in two to three years [1]. Repeat testing may be warranted earlier (one to two years) in patients with more severe disease requiring prolonged corticosteroid therapy or less frequently (three to five years) in patients with mild disease.
Patients with low bone mass on initial evaluation require further assessment.
Laboratory evaluation — In patients who have low bone mass, laboratory evaluation may help identify other causes of osteoporosis, such as renal or liver disease, vitamin D deficiency, and hyperparathyroidism (table 3).
Patients with a history of a low trauma fracture or low bone mass (T-score below -2.5 for postmenopausal women and men ≥50 years or Z-score below -2.0 for premenopausal women and men <50 years) should have the following basic tests:
●Biochemistry profile (especially calcium, phosphorous, albumin, total protein, creatinine, liver enzymes including alkaline phosphatase, electrolytes)
●25-hydroxyvitamin D
●Complete blood count
●Testosterone (men only)
Measuring urinary calcium excretion (24-hour collection for calcium and creatinine) may identify patients with severe malabsorption (low urinary calcium level) and may be useful for monitoring response to calcium supplementation.
Patients who have abnormalities on the initial laboratory testing or who have suspicious findings on history and physical examination may also require additional laboratory tests (table 4). The evaluation of osteoporosis is reviewed in detail separately. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'Evaluation' and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men", section on 'Evaluation'.)
TREATMENT — There are limited data on the prevention and treatment of low bone mass in patients with IBD. The approach outlined below is developed from guidelines for the prevention and treatment of osteoporosis in postmenopausal women, men, and in patients taking glucocorticoids. Most important is to use the lowest dose of glucocorticoid that controls the IBD. (See "Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)
The treatment of low bone mass in patients with IBD includes lifestyle measures; correction of gonadal steroid and vitamin D deficiency, if these problems exist; minimizing glucocorticoid dose, duration, and type; and pharmacologic therapy, if necessary.
Lifestyle measures — Patients with IBD should adopt the same lifestyle measures that are recommended for all patients at risk for osteoporosis and fracture. These include regular weightbearing exercise, cessation of smoking, limiting alcohol intake, and preventing falls. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Lifestyle measures' and "Treatment of osteoporosis in men", section on 'Lifestyle measures'.)
Physical activity and gravitational forces are important determinants of bone health, and physical activity can increase bone mineral density (BMD) in patients with osteopenia. In a 12-month trial of low-impact versus no exercise in 117 patients with Crohn disease (CD), nonsignificant gains in BMD occurred at the hip and spine in the group randomly assigned to the exercise program [36]. Patients were asked to exercise at least twice a week and at least 10 times per month. Increases in BMD were significantly related to the number or exercise sessions completed.
Calcium and vitamin D — Vitamin D insufficiency and calcium malabsorption are common in patients with IBD. (See "Vitamin and mineral deficiencies in inflammatory bowel disease", section on 'Vitamin D' and "Vitamin and mineral deficiencies in inflammatory bowel disease", section on 'Calcium'.)
There are limited data on the skeletal effects of calcium and vitamin D supplementation in patients with IBD and low bone mass [37,38]. As a general rule, patients with IBD and low bone mass should receive standard amounts of calcium (1200 mg/day, total diet plus supplement) and vitamin D (800 to 1000 international units/day [20 to 25 micrograms/day]). In some meta-analyses, supplementation with calcium and vitamin D has been shown to reduce fracture risk in men and women. (See "Calcium and vitamin D supplementation in osteoporosis".)
When considering vitamin D and calcium supplementation in patients with IBD, several important factors merit special attention:
●Vitamin D (800 to 1000 international units/day [20 to 25 micrograms/day]) and calcium (1200 mg/day) should be sufficient to minimize bone loss in patients with ulcerative colitis (UC) but not necessarily in patients with extensive CD of the small bowel, since the latter may have poor absorption of calcium. In such patients, the adequacy of the calcium and vitamin D supplementation should be assessed by measurements of serum and urinary calcium, serum albumin, 25-hydroxyvitamin D, and parathyroid hormone (PTH).
●Calcium citrate should generally be used instead of calcium carbonate because it may be absorbed better. (See "Calcium and vitamin D supplementation in osteoporosis".)
●The citrate and carbonate components of supplemental calcium compounds provide bicarbonate precursors that have two additional advantages in patients with IBD; they can correct the metabolic acidosis that may result from persistent diarrhea and reduce the tendency to urolithiasis, which is increased in these patients (see "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults", section on 'Extraintestinal manifestations'). The reduction in stone formation is due to increased binding of oxalate in the intestinal lumen, increased urinary citrate excretion (citrate complexes with calcium to form a soluble product), and the rise in urine pH, which increases the solubility of uric acid. (See "Kidney stones in adults: Epidemiology and risk factors".)
Gonadal steroid replacement — High doses of glucocorticoids inhibit the secretion of gonadotropins and thereby reduce the production of gonadal steroids. A woman of premenopausal age with IBD who has amenorrhea or severe oligomenorrhea should therefore be evaluated for hypogonadism by measurement of serum estradiol and gonadotropins. If hypogonadism is confirmed, she should be offered treatment with estradiol transdermally and a progestin orally (cyclically) or an oral contraceptive pill, if not contraindicated. (See "Evaluation and management of secondary amenorrhea", section on 'Initial evaluation' and "Treatment of hypopituitarism", section on 'Women'.)
However, results from a large, prospective, randomized trial of estrogen and progestin replacement therapy in otherwise healthy postmenopausal women documented an increased risk of adverse effects, including breast cancer, myocardial infarction, and stroke in those receiving combination estrogen-progestin therapy [39]. Thus, bisphosphonates should be used instead of estrogen and progestin in postmenopausal women. (See "Menopausal hormone therapy: Benefits and risks" and 'Pharmacologic therapy' below.)
High-dose glucocorticoid therapy can also lower serum testosterone concentrations in men [30], so men with IBD who take glucocorticoids should have periodic measurements of serum testosterone, and testosterone therapy should be offered if the concentration is low. (See "Clinical features and diagnosis of male hypogonadism" and "Testosterone treatment of male hypogonadism".)
Pharmacologic therapy
Candidates for therapy — There are few data that inform the decision as to which patients with IBD should receive pharmacologic therapy for bone disease [2]. In the absence of data specifically in patients with IBD, recommendations for therapy are based upon data in men and postmenopausal women with osteoporosis and in patients receiving high-dose glucocorticoids. (See "Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)
Patients with the highest risk for fracture, based on BMD and clinical risk factors, are the ones most likely to benefit from drug therapy.
●Men >50 years and postmenopausal women with IBD and established osteoporosis (history of fragility fracture or BMD T-score ≤-2.5) are candidates for pharmacologic therapy as are similar men and women without IBD.
●Men >50 years and postmenopausal women without established osteoporosis should be assessed using the Fracture Risk Assessment Tool (FRAX). In the United States, a reasonable cutpoint to indicate high risk is a 10-year probability of hip or combined major osteoporotic fracture of ≥3 and 20 percent, respectively. Fracture risk assessment, including the FRAX tool and its limitations, is reviewed in detail separately. (See "Osteoporotic fracture risk assessment", section on 'Fracture risk assessment tool'.)
●Men >50 years and postmenopausal women who have a FRAX-calculated absolute risk below these cutpoints, who are receiving ≥7.5 mg/day of prednisone or its equivalent for an anticipated duration of ≥3 months, are also candidates for therapy.
The FRAX tool was not developed for use in premenopausal women or men <40 years. Fracture risk in these patients with IBD is not clearly defined, so treatment must be extrapolated from data in premenopausal women and men taking high-dose glucocorticoids. These recommendations are reviewed in detail elsewhere. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Premenopausal women and younger men'.)
One area of uncertainty is the selection of hypogonadal men, who are already treated with testosterone therapy, for additional pharmacologic therapy. There are no clinical trial data that address this question and, in particular, the effect of testosterone on fracture risk has not been evaluated. For hypogonadal men who are at high risk for fracture (eg, chronic high-dose glucocorticoid therapy), we suggest the addition of pharmacologic therapy to testosterone therapy. The rationale for this recommendation is reviewed in detail elsewhere. (See "Treatment of osteoporosis in men", section on 'Candidates for therapy' and "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Candidates for pharmacologic therapy'.)
Choice of therapy — In small, randomized trials in men and pre- and postmenopausal women with IBD, bisphosphonates have been shown to prevent bone loss [40-42]. These trials were not designed to assess fracture as a primary outcome. Nevertheless, for men and postmenopausal women with IBD who are candidates for therapy, we suggest oral bisphosphonates as the first-line pharmacologic option.
Although there are no trials comparing the relative efficacy of the individual bisphosphonates, we prefer alendronate or risedronate given orally once a week. Intravenous (IV) zoledronic acid is a good option for those who cannot tolerate or absorb bisphosphonates orally.
For premenopausal women with fractures or accelerated bone loss who do not need estradiol replacement because they have normal menstrual function, we generally suggest bisphosphonates. However, it is important to consider the potential for harm to the fetus in women who become pregnant who are currently receiving or were recently treated with bisphosphonates. (See "Evaluation and treatment of premenopausal osteoporosis", section on 'Antiresorptive therapy with bisphosphonates'.)
Recombinant PTH (teriparatide) or denosumab could be considered for patients with IBD and osteoporosis who are intolerant of any bisphosphonate or who fail bisphosphonate therapy (fracture with loss of BMD in spite of compliance with therapy), or who have especially severe osteoporosis, although there are no data about use of these drugs in IBD. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)
Efficacy
Bisphosphonates — Bisphosphonates attenuate corticosteroid-induced bone loss, so they are frequently used for the prevention and treatment of osteoporosis in patients taking corticosteroids. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Bisphosphonates'.)
Because corticosteroid treatment is a risk factor for IBD-associated bone loss, bisphosphonates are also frequently used for the prevention of bone loss in patients with IBD. In several small, clinical trials in men and pre- and postmenopausal women with IBD, oral bisphosphonates were shown to improve BMD compared with placebo [40-42]. As an example, in a 12-month trial of risedronate (35 mg weekly) versus placebo in 90 postmenopausal women with IBD in remission, BMD (lumbar spine, trochanter, and femoral neck) significantly increased in the risedronate group compared with placebo [42]. The incidence of vertebral fractures, a secondary endpoint, was significantly lower in the risedronate group (12.5 versus 34 percent).
IV bisphosphonates are an alternative option for patients unable to tolerate or absorb oral bisphosphonates. In a small trial, IV ibandronate (1 mg every three months) significantly improved BMD in patients with CD [43]. (See "Bisphosphonate therapy for the treatment of osteoporosis", section on 'Choice of bisphosphonate'.)
IV zoledronic acid reduces bone loss and fracture in postmenopausal women with osteoporosis, reduces recurrent fracture in men and women with hip fracture, and reduces bone loss in corticosteroid-induced osteoporosis. It is likely effective in patients with IBD, but such data are not yet available. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Bisphosphonates' and "Bisphosphonate therapy for the treatment of osteoporosis", section on 'Choice of bisphosphonate'.)
Bisphosphonates should be used with caution in premenopausal women because of insufficient information on the potential for harm to the fetus in women who become pregnant while currently or recently receiving bisphosphonates. In these patients who require drug treatment, long-lasting drugs like zoledronic acid and alendronate should be avoided in favor of drugs that accumulate less (such as risedronate or denosumab) or not at all (such as PTH) [44]. (See "Evaluation and treatment of premenopausal osteoporosis", section on 'Antiresorptive therapy with bisphosphonates'.)
The dosing, side effects, and contraindications of bisphosphonates are reviewed separately. (See "Bisphosphonate therapy for the treatment of osteoporosis", section on 'Practical management issues'.)
Parathyroid hormone — PTH stimulates bone formation as well as resorption, and intermittent administration stimulates formation more than resorption. Although there are no clinical trials of PTH for the treatment of osteoporosis in patients with IBD, several trials show that it is beneficial in patients with osteoporosis. (See "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis".)
This benefit also appears to apply to patients with glucocorticoid-induced osteoporosis. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Parathyroid hormone' and "Evaluation and treatment of premenopausal osteoporosis".)
In the absence of any clinical trial data with teriparatide versus bisphosphonates in patients with IBD, we typically reserve the use of teriparatide for patients with severe osteoporosis and fracture who are not candidates for or are intolerant of bisphosphonates.
SUMMARY AND RECOMMENDATIONS
●Patients with inflammatory bowel disease (IBD) are at risk for osteoporosis and fracture for several reasons, including disease-related inflammatory activity, glucocorticoid therapy, hypogonadism, and nutritional deficiencies. Advanced age and low body mass index (BMI) further increase risk. (See 'Risk factors' above.)
●The goal of the clinical evaluation is to identify patients with IBD who are at high risk for bone loss and fracture. We perform a history and physical examination to elicit clinical risk factors for fracture (table 1). We obtain a bone mineral density (BMD) study (dual-energy x-ray absorptiometry [DXA] spine and hip) in patients with IBD who are at higher risk for osteoporosis and fracture (previous fragility fracture, postmenopausal, male >50 years, hypogonadism, or chronic [>3 months] glucocorticoid therapy). (See 'Assessment of clinical risk for fracture' above.)
●Patients with a history of a fragility fracture or low bone mass by initial DXA require laboratory evaluation to identify possible secondary causes of osteoporosis (table 3 and table 4). (See 'Laboratory evaluation' above.)
●We counsel patients with IBD and low bone mass about lifestyle behaviors that will improve their bone health, including exercise, stopping smoking, means of preventing falls, and avoiding heavy alcohol use. (See 'Lifestyle measures' above.)
●We suggest calcium and vitamin D supplementation in patients with IBD, low bone mass, and inadequate dietary intake (Grade 2B). Although the optimal total intake (diet plus supplement) has not been clearly established in this patient population, approximately 1200 mg of calcium and 800 to 1000 international units (20 to 25 micrograms) of vitamin D daily are the typical doses used in patients with low bone mass. (See 'Calcium and vitamin D' above.)
Patients with malabsorption may require higher doses of calcium and vitamin D. Adequacy of the dose can be assessed by measuring serum and urinary calcium, albumin, parathyroid hormone (PTH), and 25-hydroxyvitamin D. (See 'Calcium and vitamin D' above and "Calcium and vitamin D supplementation in osteoporosis", section on 'Underlying gastrointestinal disease'.)
We generally use calcium citrate, which is better absorbed than calcium carbonate, in patients with IBD.
●Estrogen-progestin replacement therapy (if not contraindicated) is generally initiated in premenopausal women with IBD and menstrual irregularities while taking glucocorticoids. Testosterone replacement therapy (if not contraindicated) is generally initiated in men with IBD and symptomatic hypogonadism. (See 'Gonadal steroid replacement' above and "Evaluation and treatment of premenopausal osteoporosis" and "Clinical features and diagnosis of male hypogonadism" and "Testosterone treatment of male hypogonadism".)
●For postmenopausal women and for men >50 years of age with IBD and T-scores below -2.5 or history of a fragility fracture, we recommend pharmacologic therapy (Grade 1A). (See 'Candidates for therapy' above.)
●For high-risk postmenopausal women and men >50 years of age with IBD and T-scores between -1.0 and -2.5, we also suggest pharmacologic therapy (Grade 2B). Our definition of high risk, which also may be cost effective in some settings, is a Fracture Risk Assessment Tool (FRAX) 10-year probability of hip or combined major osteoporotic fracture of ≥3 or 20 percent, respectively. (See 'Candidates for therapy' above.)
●For postmenopausal women and men >50 years with IBD who have lower risk by FRAX, we suggest pharmacologic therapy if they are taking ≥7.5 mg/day of prednisone or its equivalent for an anticipated duration of ≥3 months (Grade 2C). (See 'Candidates for therapy' above.)
●There are few data that inform the decision as to which premenopausal women and men <50 years with IBD should receive pharmacologic therapy for bone disease. Recommendations for this population are extrapolated from limited data in premenopausal women and younger men taking glucocorticoids. These recommendations are reviewed in detail elsewhere. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Premenopausal women and younger men'.)
●For pharmacologic therapy, we suggest bisphosphonates as first-line therapy (Grade 2B). Selective estrogen receptor modulators (postmenopausal women), PTH (men and women), and denosumab (men and postmenopausal women) have been shown to be effective for the treatment of osteoporosis, so they are options, but they have not been studied in patients with IBD. (See 'Pharmacologic therapy' above and "Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men" and "Evaluation and treatment of premenopausal osteoporosis".)
Medical therapy in premenopausal women with IBD should take into account the insufficient information on the potential for harm to the fetus in women who become pregnant while taking bisphosphonates shortly after discontinuing them.
●We prefer weekly oral alendronate or risedronate. Intravenous (IV) bisphosphonate formulations are available for patients who cannot tolerate or absorb oral bisphosphonates or who have difficulty with dosing requirements. (See 'Choice of therapy' above.)
ACKNOWLEDGMENT — We are saddened by the death of Paul Rutgeerts, MD, who passed away in September 2020. UpToDate gratefully acknowledges Dr. Rutgeerts' work as our Section Editor for Gastroenterology.
