Beclomethasone

Limits on what this shows

• Null findings: Luengo 1991 [18]: asthmatics on chronic BDP 585 +/- 210 mcg/day (range 400 to 1,200; 25 per asthma group by implication) showed no serum PTH difference from healthy subjects, and the authors concluded these regimens did not cause calcium malabsorption. Calcium absorption values and method were not retrievable from the reconstructed abstract, and the healthy-control n is not stated. Kwda 2019 [19]: 70 children on long-term BDP versus 70 controls, serum calcium not different (p = 0.554). Konig 1993 [28] (opened at the repair, abstract-level, two records agree): children with asthma on inhaled BDP 300 to 800 mcg/day for at least 6 months (mean 25 months), 18 matched pairs plus 8 more pairs and 61 healthy children for comparison; serum calcium, magnesium, zinc, PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and urinary calcium excretion did not differ between BDP-treated and untreated asthmatic children, and bone mineral density and content did not differ either; numeric values were not in the abstract. Boulet 1994 [15]: serum calcium and urinary calcium were measured in 74 adults on BDP or budesonide; the abstract reports no calcium difference (only osteocalcin and urinary phosphorus differed).
• At-risk subgroups: People who swallow a large share of an inhaled dose (no spacer, no mouth rinse, high dose) and people with low calcium intake. In 58 adults on BDP, lumbar BMD correlated with calcium intake (r = 0.40, P <.02) [16]; that is an intake correlation, not a drug effect.

Regulatory status

Neither retrieved label mentions calcium or vitamin D. The QVAR REDIHALER label (sections 5.9, 12) addresses reduced bone mineral density only and says the clinical significance for fracture is unknown [1]. The QNASL label has no bone, calcium or vitamin D text in the retrieved extract [2].

Population evidence

Smith 1993 [17]: randomized, double-blind, placebo-controlled crossover, 12 healthy volunteers (all completed), BDP 500 mcg twice daily as swallowed capsules (1,000 mcg/day) versus placebo, one week each. Full text (journal PDF) read at the 2026-10-08 repair: strontium absorption, the calcium absorption proxy, was 9.7% (SD 2.1) of the dose on BDP versus 11.0% (SD 2.0) on placebo, p under 0.01, a mean 12% reduction, lower in 11 of 12 subjects; 24-hour urinary cortisol was 147 (SD 45) versus 191 (SD 40) nmol/day, p under 0.0005, a 23% reduction. No confidence interval is printed. Serum PTH (43.9 versus 44.3 pmol/l), plasma calcium (2.38 mmol/l in both weeks), urinary calcium (2.79 versus 3.00 mmol/day) and urinary hydroxyproline (210 versus 222 umol/day) did not differ; plasma phosphate rose in the first BDP week in one sequence group (p under 0.05). The authors note a possible incomplete washout in the BDP-first sequence, where absorption rose only 3.2% (not significant) in the placebo week.

Mechanism

Proposed by the authors: most of a metered-dose inhaler dose is swallowed, and in the intestinal lumen BDP is hydrolysed to beclomethasone-17-monopropionate, which has much greater glucocorticoid receptor affinity, so a topical effect on intestinal calcium absorption is possible; the authors state they cannot be sure how much of the effect is topical versus systemic [17]. The 23% fall in urinary cortisol shows that systemic exposure also occurred, so a local gut effect cannot be separated from a systemic corticosteroid effect in this trial (this separation is the dossier's inference, not the authors' claim). Beclomethasone-17-monopropionate, the active metabolite, is more than 90% of systemic drug after inhalation and 94 to 96% protein bound [1].

Why orange, not red

Red needs two independent Tier A sources with calcium directly measured and consistent direction. There is one positive source (oral route, 1 week) and two null sources at inhaled doses. Kwda and Luengo contradict the inhaled-dose version of the claim. A second positive cohort was not found. The Konig 1993 pediatric BDP bone-metabolism paper (PMID 8429434), opened at the repair, adds a further Tier A null (serum calcium, PTH, vitamin D metabolites and urinary calcium unchanged on 300 to 800 mcg/day inhaled) and so does not supply a second positive source [28]. The Smith companion markers (PTH, plasma and urinary calcium) were unchanged in the one-week window, so the finding is a functional absorption change without a measured circulating or hormonal consequence.

Counter-evidence held on record

Counter-evidence and confounding Not a clinical outcome: calcium absorption itself was measured, so Hard Rule 2 is met. The effect size is small (9.7% versus 11.0% of dose absorbed, a 1.3 percentage point difference), the design is short, and the route (oral capsules) differs from labeled use. The popular claim that corticosteroids deplete calcium traces to systemic-steroid trials [26] and is not tested for inhaled BDP by those sources. Fracture and low BMD are outcomes and are handled in the BMD entry. Framing caution This is a bounded, short-term absorption finding from swallowed capsules, not evidence that usual inhaled or nasal use depletes calcium. It is not a reason to add calcium. No supplement dose is given here; any calcium or vitamin D decision belongs with a prescriber or pharmacist.

Limits on what this shows

• Null findings: Nasal route at labeled doses shows cortisol ratios whose confidence intervals include 1 [2]. Fewer than 1% abnormal cosyntropin responses in the one-year inhaled study [1].
• At-risk subgroups: Higher dose, longer duration, transfer from systemic steroids (label reports adrenal insufficiency deaths during and after such transfers) [1].

Regulatory status

QVAR REDIHALER label, sections 5 and 12.2 [1]: hypercorticism and adrenal suppression may occur, mainly at above-recommended doses over prolonged periods; 24-hour urinary free cortisol fell 12.2%, 24.6% and 37.3% across three QVAR doses (40 corticosteroid-naive patients) versus 47.3% for CFC-BDP 336 mcg twice daily; in a one-year open-label study of 354 patients, fewer than 1% had an abnormal cosyntropin response. The label's dose columns are internally inconsistent in the retrieved extract. QNASL label [2]: 24-hour serum cortisol geometric mean ratio versus placebo 0.96 (95% CI 0.87 to 1.06) in adults on 320 mcg/day and 0.91 (0.81 to 1.03) in children aged 6 to 11 on 80 mcg/day; a prednisone 10 mg/day positive control gave a ratio of 3.17 (2.68 to 3.74), direction as reported in the extract.

Population evidence

Martin 2002 [21]: 156 steroid-naive adults, one-week dose-doubling design; the BDP-CFC dose producing 10% cortisol suppression was 548 mcg/day (flunisolide 936, triamcinolone 787, fluticasone DPI 445, budesonide DPI 268, fluticasone CFC 111). Grebe 1997 [22]: 21 BDP users versus 21 matched controls; lower 24-hour urinary free cortisol (P < 0.008) and lower stimulated cortisol, inversely related to dose, about 15% with clinically significant suppression. Kwda 2019 [19]: cortisol suppression on low-dose synacthen testing in 24% of 70 children on BDP; longer duration (p < 0.01) and higher dose (p < 0.001) associated. Lipworth 1999 meta-analysis [20]: 27 studies, marked suppression above 1.5 mg/day of inhaled steroid; fluticasone more potent than BDP.

Mechanism

Present for the hormone effect: systemic exposure to beclomethasone-17-monopropionate acting as a glucocorticoid [1]. No nutrient is implicated by this entry.

Why yellow

The grade encodes causal attribution of a nutrient deficiency to the drug. None is claimed. The underlying hormone effect has multiple Tier A sources with BDP in the cohort, which is why it is carried as a context flag rather than omitted.

Counter-evidence held on record

Counter-evidence and confounding Cortisol output is an endocrine measure, not a nutrient level. Confounding by prior oral steroid courses is possible in observational cohorts [22]. Suppression of the axis is a marker, and its link to effects in other organs remains uncertain per the Grebe authors [22]. Framing caution Do not present adrenal suppression as a nutrient deficiency. The consumer-facing message is a prescriber conversation about the lowest effective dose and not stopping abruptly; no supplement is implied.

Limits on what this shows

• Null findings: Baraldi 1994 [14]: 14 children on BDP 300 to 400 mcg/day via spacer versus 16 untreated controls for 6 months, no height velocity difference. Kwda 2019 [19]: all 70 BDP-treated children within mid-parental height range at follow-up, no numeric height data. Lipworth 1999 [20]: growth suppression at 400 mcg/day BDP in medium-term studies but no evidence of reduced final adult height.

Regulatory status

QVAR REDIHALER label sections 5.8 and 8.4 [1]: orally inhaled corticosteroids may reduce growth velocity; routine growth monitoring advised. In a 12-month randomized trial of QVAR MDI versus CFC-BDP by large-volume spacer in 520 children aged 5 to 11 (394 and 126), growth velocity on QVAR was about 0.5 cm/year lower than CFC-BDP; adult height effects and catch-up growth are unknown. The QNASL label states a growth reduction cannot be ruled out and cites the same QVAR trial [2].

Population evidence

Sharek 2000, Pediatrics meta-analysis [5]: BDP subgroup of 4 randomized trials, 450 subjects, growth velocity reduced by 1.51 cm/year (95% CI 1.15 to 1.87) versus non-steroid control; sensitivity analyses on quality, delivery mode, control and model were similar (abstract reconstructed from OpenAlex). Sharek and Bergman, Cochrane 2000 [6]: 3 randomized trials, BDP 200 mcg twice daily by dry powder inhaler, 7 to 12 months, average decrease of 1.54 cm/year versus placebo or non-steroid therapy (summary via fetch tool). These two reviews share authors and overlapping trials and are one line of evidence, not two. Skoner 2000 [7]: double-blind randomized, 100 prepubertal children with perennial allergic rhinitis, intranasal aqueous BDP 168 mcg twice daily (n = 51) versus placebo (n = 49) for 1 year; mean height gain 5.0 cm versus 5.9 cm (a 0.9 cm difference computed from the two reported means; confidence interval and p value not in the reconstructed abstract). Axelsson 2019 Cochrane [8]: BDP by HFA-MDI and CFC-MDI performed comparably on growth; fluticasone was associated with greater growth velocity than BDP in one small trial (low certainty).

Mechanism

Present, pharmacologic: systemic glucocorticoid exposure from the active metabolite [1].

Class extrapolation note

CLASS EXTRAPOLATION, not used for grading: Mener 2015 meta-analysis of intranasal corticosteroids [9] (8 randomized trials, 755 children) found stadiometry -0.053 cm/year (95% CI -0.491 to 0.385) and knemometry -0.223 mm/week (-0.429 to -0.017). The retrieved abstract does not name BDP, so the cohort test is not passed for this drug; it is reported only as context against the Skoner result.

Counter-evidence held on record

Counter-evidence and confounding Growth velocity is a clinical outcome with many competing explanations (asthma severity, atopy, pubertal timing, prior oral steroid courses). Study durations were 54 weeks or less [5][6], so persistence is unknown. Framing caution Do not file growth as a nutrient deficiency or imply that nutrition or supplements correct it. The consumer-facing prompt is height monitoring with a prescriber and use of the lowest effective dose.

Limits on what this shows

• Null findings: Medici 2000 [13]: 69 adults, BDP 800 mcg/day (n = 21) or 1,500 mcg/day (n = 13) versus fluticasone, 1 year, peripheral QCT showed no loss of trabecular or integral density at radius or tibia in any group. Boulet 1994 [15]: 37 adults on BDP or budesonide 800 mcg/day or more (mean 1,140 mcg/day) versus 37 on under 500 mcg/day; lumbar BMD 0.923 versus 0.933 g/cm2 and hip 0.719 versus 0.694 g/cm2, both p > 0.05; osteocalcin 2.16 versus 2.70 ng/mL (p = 0.029); no dose or duration correlation. Gagnon 1997 [16]: 58 completers, BMD not different between high- and low-dose BDP groups. Baraldi 1994 [14]: children on BDP 300 to 400 mcg/day, lumbar bone mineral rose about 2.3% in BDP versus about 4% in controls over 6 months (assignment inferred from a truncated abstract), authors concluded no significant influence.

Regulatory status

QVAR REDIHALER label section 5.9 [1]: decreases in BMD have been observed with long-term inhaled corticosteroids; clinical significance for fracture is unknown; patients with major osteoporosis risk factors should be monitored. QNASL label: no bone loss text in the retrieved extract [2].

Population evidence

Richy 2003 [10]: meta-analysis, 23 trials identified and 11 papers in the main analysis, asthma and COPD patients; BMD effect size 0.27 (p < 0.001), lumbar spine 0.21 and hip 0.26; bone formation markers (osteocalcin, PICP) fell; budesonide least deleterious, then BDP, then triamcinolone; BDP mean dose 703 mcg/day (SD 123); per-drug effect sizes were not in the abstract (summary via fetch tool). Egan 1999 [12]: 33 adults randomized to BDP 2,000 mcg/day or fluticasone 1,000 mcg/day for 2 years (9 BDP completers); fluticasone stable, BDP showed some decline in vertebral trabecular BMD by quantitative CT, between-group p = 0.006 (and p = 0.004 at 24 months); numeric BMD values not retrieved. Ebeling 1998 [11]: 53 adults on BDP or budesonide at 1,500 mcg/day or more for 12 months or more; prior oral glucocorticoid users had about 1 SD lower BMD than inhaled-only users; bone formation markers lowered, resorption markers normal; not stratified by drug.

Mechanism

Present, pharmacologic (systemic glucocorticoid effect, lower bone formation markers) [10][11]. No nutrient mechanism is established here.

Counter-evidence held on record

Counter-evidence and confounding Confounders are strong: prior oral steroid courses (Ebeling about 1 SD difference [11]), disease severity, smoking and activity. Several cohorts pooled BDP with budesonide [11][15][16], so BDP is in the cohort but not separable. Egan compared against an active comparator, which does not test BDP against non-use [12]. Fracture significance is unknown per the label [1]. Framing caution Low BMD is an outcome, not a vitamin D or calcium deficiency. The consumer-facing prompt is a bone-health conversation for people with other osteoporosis risk factors; no supplement is implied by this entry.

Limits on what this shows

• Null findings: The Kwda comparison itself is the null. Gagnon 1997 [16] recorded vitamin D intake from 3-day food diaries in 58 adults on BDP, but the abstract reports no vitamin D result. Konig 1993 [28] (second pediatric BDP cohort, same shared record as the calcium entry): serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D did not differ between children on BDP 300 to 800 mcg/day and untreated asthmatic children; numeric values were not in the abstract.

Regulatory status

Not mentioned in either retrieved label extract [1][2]. Label section 5.9 names corticosteroids as drugs that reduce bone mass but does not address vitamin D or calcium supplementation [1].

Population evidence

Kwda 2019 [19]: 70 children with asthma on long-term inhaled beclomethasone (daily dose grouped low 100 to 200 mcg, medium 200 to 400, high above 400; distribution 56%, 32%, 12%) versus 70 age- and sex-matched non-ICS controls. Vitamin D profile did not differ (p = 0.187); vitamin D below 50 nmol/L in 34% of ICS-treated and 41% of control children. Alkaline phosphatase was measured but values were not in the abstract. Whether any child used another inhaled steroid is not stated in the abstract.

Mechanism

Absent in retrieved BDP evidence. No study of 17-BMP effects on vitamin D handling (for example CYP24A1 induction) was retrieved.

Why yellow and not ungraded or white

This is a context flag for high baseline prevalence in the treated population, which Step 7 assigns to yellow. It is not white because the only drug-specific datum is a null from a single cohort with unknown ICS identity beyond beclomethasone dosing, and no circulating claim about BDP and vitamin D was found to rebut.

Counter-evidence held on record

Counter-evidence and confounding Confounding by indication is presumed: asthma, reduced outdoor activity and sun exposure, and age independently lower vitamin D. Insufficiency in 41% of controls shows that the prevalence is not drug caused. Cross-sectional design; no PTH reported. Framing caution This is not a depletion claim. It is a monitoring prompt about baseline status only. No supplement or dose is recommended.

Limits on what this shows

• Null findings: Skoner 2000 [7]: 100 children, intranasal BDP 336 mcg/day for 1 year; no clinically meaningful changes in fluid and electrolyte, protein, lipid or carbohydrate metabolism (reconstructed abstract).

Regulatory status

Neither retrieved label mentions hyperglycemia or glucose [1][2].

Population evidence

Kruszynska 1987 [23]: open design, 9 normal subjects, inhaled BDP 500 mcg twice daily for 4 weeks. Fasting glucose and glycosylated hemoglobin unchanged; peak glucose 30 minutes after a 75 g load 7.1 (SEM 0.2) versus 6.7 (0.1) mmol/L; fasting insulin up 36% (5.6 to 7.6 mU/L) and insulin area under the curve up 32%; total cholesterol 4.16 to 4.62 mmol/L and HDL 0.97 to 1.19 mmol/L; lactate and pyruvate higher, glycerol lower. p values were not in the reconstructed abstract.

Mechanism

Present for the hormone effect: glucocorticoid-induced insulin resistance. Mechanism text was not separately retrieved; the finding itself is the evidence.

Counter-evidence held on record

Counter-evidence and confounding Glucose is a metabolic marker, not a nutrient, and the study is small, open-label and of normal volunteers at 1,000 mcg/day, above usual maintenance doses. The Tier D chromium claim [26] depends on this kind of glucose effect; see Fails verification. Framing caution Do not file glucose handling as a nutrient deficiency, and do not suggest chromium or any supplement. A person with diabetes on inhaled steroids should follow their prescriber's monitoring plan.

Limits on what this shows

• Null findings: Skoner 2000 [7]: no meaningful change in protein metabolism after 1 year of nasal BDP. Oropharyngeal pain is among the most common adverse reactions above placebo in adults and adolescents [1]; no weight loss or dysphagia signal appeared in the retrieved label extracts.

Regulatory status

QVAR REDIHALER label [1]: localized Candida albicans infection of the mouth and pharynx can occur; patients are advised to rinse with water without swallowing. Adverse reaction table: oral candidiasis 0 at the lowest dose (N = 90), 3% (7 of 214) and 7% (15 of 211) at higher doses versus under 1% on placebo (1 of 304); the extract notes that the table's dose labels do not match the dosing text. QNASL label [2]: Candida infection of nose and pharynx was reported with an earlier aqueous beclomethasone product and not seen in QNASL trials; periodic examination advised.

Population evidence

Gagnon 1997 [16] (PubMed record via fetch tool): 74 recruited and 58 completed; 31 with moderate to severe asthma on more than 1,000 mcg/day beclomethasone (or equivalent) for over 2 years versus 27 with mild asthma on under 500 mcg/day. 3-day food diaries; protein intake was lower in the moderate to severe group (P <.05) and BMD was not different between groups. Calcium, phosphorus, magnesium, zinc and vitamins A, C and D intakes were analyzed but the abstract reports no results for magnesium, zinc or vitamin D.

Mechanism

Present as a pathway (pain or taste change from oral candidiasis could lower intake); no intake data tied to candidiasis were found. Not demonstrated.

Counter-evidence held on record

Counter-evidence and confounding The Gagnon protein difference compares disease severity groups, so confounding by indication is presumed: sicker patients on higher doses eat differently. The two groups were also not randomized. Framing caution Context flag only. It is not a finding that BDP lowers intake of any nutrient. Rinsing the mouth after use is the labeled mitigation; no supplement is implied.

Limits on what this shows

• Null findings: Del Rio-Navarro [29] and Skoner [7], above. Excluded: Sharma 2003 [37] (Indian J Pediatr, PMID 12661806, 57 children in acute asthma) reports a larger serum potassium fall with salbutamol plus BDP than salbutamol alone when no spacer was used, but it has no BDP-only arm and the beta-agonist is the known potassium-lowering component, so it cannot attribute anything to BDP; it was read at abstract level only and is not used for grading.

Regulatory status

Neither retrieved label extract mentions hypokalemia or potassium [1][2]. Hypokalemia with combination inhalers comes from the beta-agonist component and is outside this single-agent dossier.

Population evidence

BDP, Tier A, null: Del Rio-Navarro 2001 [29], prospective randomized open crossover, 29 children with asthma (20 boys, mean age 11 years), BDP 100 mcg per puff, 2 puffs every 12 hours (400 mcg/day) for 6 weeks versus BDP plus salmeterol, 4-week washout. Serum potassium baseline 4.57 (SD 0.43) mEq/L, after BDP 4.38 (SD 0.39), after BDP plus salmeterol 4.38 (SD 0.40); the authors report no change in potassium or QTc. The journal page prints a different baseline (4.43) from the PubMed abstract (4.57); both records agree on the post-BDP value and the conclusion. Skoner 2000 [7]: 100 children, 1 year of intranasal BDP, no clinically meaningful change in fluid and electrolyte metabolism (reconstructed abstract). Class source, Tier C: Mohn 2018 [27], section 2.9.2 on oral corticosteroids, states that corticosteroids can cause sodium and water retention and raise potassium excretion, with the mechanism not fully understood; its references 344 to 349 were not opened.

Class cohort test

CLASS EXTRAPOLATION. The review section concerns oral (systemic) corticosteroids; the drugs behind references 344 to 349 are not identified in the text read, and beclomethasone is not named anywhere in the section. This drug was not in the cohort of the class source, so the entry is capped at yellow. The two BDP studies are Tier A for this drug and both are null.

Mechanism

Class-level renal potassium wasting (Mechanism C), described as not fully understood [27]. Applicability to inhaled or nasal BDP, which is under 10% renal (label) and has low systemic exposure, is not shown [1][2].

Counter-evidence held on record

Counter-evidence and confounding The direct BDP evidence is small (29 children, 6 weeks, moderate dose) and the sources for the class claim were not opened at the primary level. Both are weak against a clinically meaningful effect in either direction, so this entry is a plausibility flag only. Framing caution Not a finding that beclomethasone lowers potassium. This is a serum disturbance in the loss direction for systemic steroids, not a reason to raise potassium intake or to take a potassium supplement. Any potassium decision belongs with a prescriber after a measured level.