Chromium

證據等級: L5

預測適應症: 10 個

Chromium: From No Established Indication to Osteoarthritis

One-Sentence Summary

Chromium (DB11136) is an essential trace mineral with no currently registered drug indication in Singapore; as a dietary supplement, it is most commonly associated with supporting insulin sensitivity and glucose metabolism. The TxGNN model predicts it may have therapeutic value for Osteoarthritis, with 1 terminated Phase 2 trial and 20 retrieved publications — the vast majority of which concern chromium as a wear product from metal joint implants rather than as a therapeutic agent. This distinction represents a fundamental evidence quality issue, and the overall recommendation is Hold pending clarification of the terminated trial and a dedicated mechanistic evidence base.

Quick Overview

Item	Content
Original Indication	No registered drug indication
Predicted New Indication	Osteoarthritis
TxGNN Prediction Score	98.68%
Evidence Level	L3
Singapore Market Status	✗ Not marketed
Number of Registrations	0
Recommended Decision	Hold

Why Is This Prediction Reasonable?

Currently, detailed mechanism of action data for Chromium is not available in this Evidence Pack. Based on known pharmacology, trivalent chromium (Cr³⁺) is an essential trace mineral widely studied as a dietary supplement. Its proposed biological activity centres on potentiating insulin receptor tyrosine kinase signalling — an effect attributed to a low-molecular-weight chromium-binding oligopeptide (LMWCr). By improving insulin sensitivity, Cr³⁺ may theoretically dampen systemic low-grade inflammation mediated through NF-κB and downstream pro-inflammatory cytokines (TNF-α, IL-6), which are implicated in cartilage degradation and synovitis in osteoarthritis.

However, there is a critical structural problem with this TxGNN prediction: the high score likely reflects reverse causation bias in the knowledge graph. The overwhelming majority of trials and publications linking chromium to osteoarthritis arise from metal-on-metal (MoM) orthopaedic implant research, where cobalt-chromium alloy components release Cr³⁺/Cr⁶⁺ ions as wear debris — causing harm to joint tissue, not treating it. Chromium appears alongside osteoarthritis in the literature primarily as a contaminant and potential toxin, not as a beneficial agent.

The only directly relevant therapeutic trial identified (NCT00759993, Phase 2) was terminated before completion. The reason for termination is unknown from available records, which constitutes the most important unanswered question for this indication: whether stopping was due to safety signals, lack of efficacy, or administrative/funding issues will entirely determine the viability of this repurposing hypothesis.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00759993	Phase 2	Terminated	60	Chromium picolinate for prevention of serotonergic medication-induced weight gain in psychiatric inpatients; the only trial directly testing chromium supplementation in a clinical context — terminated early, reason unknown
NCT00862511	N/A	Completed	120	Serum chromium ion monitoring after coated vs. uncoated total knee arthroplasty — implant corrosion monitoring study, not chromium therapy
NCT02196792	N/A	Active, not recruiting	100	Polyethylene wear and metal ion levels in total hip replacement — monitoring study
NCT04585022	N/A	Terminated	75	Cr/Co ion concentrations in MoM hip arthroplasty at 5-year follow-up — terminated
NCT00561600	N/A	Completed	265	DePuy ASR-XL vs. Pinnacle hip system — involves voluntarily recalled implant; Cr ions monitored as safety signal
NCT05357378	N/A	Recruiting	288	HIT Reverse Hip Replacement System safety and effectiveness — new device safety study
NCT03382652	N/A	Completed	83	Continuum Metal Bearing System post-market surveillance — implant survival monitoring
NCT05815953	N/A	Active, not recruiting	60	Polarstem vs. Corail femoral stem micromotion comparison using radiostereometry — implant comparison
NCT00586781	Phase 3	Completed	21	STAR ankle replacement bilateral safety study — ankle device trial; chromium present only as implant material
NCT04058743	N/A	Terminated	8	Nickel sensitivity and TKA outcomes — metal hypersensitivity study, not chromium supplementation

⚠️ Evidence quality alert: With the sole exception of NCT00759993, all trials listed above study chromium as a component of metal implants being monitored for safety — not as a therapeutic intervention. The evidence base for chromium supplementation in osteoarthritis is essentially absent.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
34628351	2021	Observational	EBioMedicine	Differential synovial fibroblast subsets at painful vs. non-painful sites in knee OA — OA pathophysiology; no chromium link
34724103	2023	Cohort	Arch Orthop Trauma Surg	Co/Cr ion levels after MoM hip revision with dual-mobility liners — monitoring of harmful ions
37394959	2023	Cohort	Bone Joint J	Elevated serum Cr associated with worse Harris Hip Score and HOOS in ASR resurfacing patients — high Cr is detrimental
36945025	2023	Observational	J Orthop Surg Res	Cr/Co ion levels and oxidative stress markers in modular hip arthroplasty — ions linked to oxidative damage
27294138	2016	Cross-sectional	BioMed Res Int	Environmental Cr concentrations in cartilage and bone of OA patients in NW Poland — environmental exposure context
33550449	2022	Cohort	Knee Surg Sports Traumatol Arthrosc	Hypoallergenic vs. CoCr unicompartmental knee arthroplasty — return-to-sport outcomes in metal-sensitive patients
36545926	2022	RCT	Acta Orthop	Cemented vs. cementless dual mobility cups: low Co-Cr serum levels at 6 years — safety finding confirming low ion release
35926884	2022	Cohort	Can J Surg	Birmingham Hip Resurfacing: whole blood Cr/Co at 1 year vs. 10 years — long-term ion level tracking
37652450	2023	Registry/Cohort	Bone Joint J	Birmingham Hip Resurfacing 20-year survivorship — long-term implant outcomes
22325959	2012	Observational	J Arthroplasty	Co/Cr ion release after large-diameter MoM THA — significant serum ion elevation observed post-implantation

⚠️ Evidence quality alert: None of the retrieved publications directly investigate trivalent chromium supplementation as a treatment for osteoarthritis. All literature is from the metal implant monitoring domain. The reverse causation problem identified in the clinical trials is equally present in the literature.

Singapore Market Information

Chromium (DB11136) is currently not registered as a pharmaceutical product in Singapore. No marketing authorizations or product licences were identified. It may be available as an unregulated dietary supplement, but this is outside the scope of drug registration.

Safety Considerations

Please refer to the package insert for safety information.

Important valence-state distinction: Hexavalent chromium (Cr⁶⁺) is a well-established human carcinogen (IARC Group 1) and nephrotoxin. Any repurposing development must unambiguously specify trivalent chromium (Cr³⁺), which has a substantially different and more favourable safety profile. Formulation, dose, and valence state must be clearly defined before any clinical development proceeds.

Conclusion and Next Steps

Decision: Hold

Rationale: Despite a high TxGNN prediction score (98.68%), the evidence base for chromium supplementation in osteoarthritis is critically undermined by reverse causation bias — the knowledge graph signal is driven by metal implant monitoring data, not therapeutic research. The sole directly relevant clinical trial was terminated early for unknown reasons, and no completed mechanistic or efficacy studies in OA are available.

To proceed, the following is needed:

Clarify termination reason for NCT00759993: contact ClinicalTrials.gov, the FDA, or the trial investigators to determine whether termination reflected safety concerns, efficacy failure, or administrative/funding issues
Commission a dedicated systematic review on trivalent chromium supplementation in musculoskeletal inflammation, clearly excluding metal implant literature
Obtain mechanistic data (MOA) specifically addressing trivalent chromium's effect on chondrocyte metabolism, cartilage matrix, and synovial inflammation in OA models
Evaluate the Rank 3 indication (Rheumatoid Arthritis) as a higher-priority entry point: a completed Phase 2/3 RCT comparing trivalent chromium vs. baricitinib (PMID 39030450, NCT05545020) already exists with L2 evidence and a "Proceed with Guardrails" recommendation — this represents a more viable and better-supported repurposing candidate for chromium
Obtain HSA/TFDA prescribing information to assess formal safety warnings and contraindications for chromium-containing preparations
Define the proposed dosage form and administration route for any future OA indication, as no Singapore-registered formulations currently exist
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.