DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for bone resorption disease — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBone resorption disease maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for bone resorption disease is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
calcitonin receptor (CALCR) — CALCR is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8F0K · 1.9 Å · ligand (2S)-2-{[(1R)-1-hydroxyhexadecyl]oxy}-3-{[(1R)-1-hydroxyoctadecyl]oxy}propyl 2-(trimethylammonio)ethyl phosphate (P42). Experimental structure, not a prediction.
What the evidence adds up to
Twenty-four patients with unilateral orbital wall fractures received iliac crest bone grafts for reconstruction. At a mean follow-up of 7.8 months, resorption and remodelling were detected in all grafts, though none were totally resorbed. Bone defects larger than 10 mm at the reconstructed areas were found in 13 orbits (54 percent). One patient (4 percent) had both enophthalmos and hypophthalmos at the last visit; five patients (21 percent) had hypophthalmos greater than 1 mm. Scar tissue was observed in three reconstructed orbits (13 percent). Diplopia in the central field of vision resolved in all seven patients who had it preoperatively.
A 2022 prospective observational study compared 25 patients with lateral fragility femur fractures treated with clodronic acid and vitamin D after intramedullary nailing against 25 patients treated with vitamin D alone. At 12 months, the study group showed a statistically significant increase in bone mineral density in one femoral region of interest (0.93 ± 0.07 gr/cm² versus 0.88 ± 0.08 gr/cm², p = 0.04). Biochemical and densitometric values improved from baseline to 12 months in the study group, while the control group improved only in biochemical values.
A 2011 review states that zoledronic acid is standard for metastatic bone disease. Comparative trials between zoledronic acid and denosumab showed superior skeletal-related event prevention for denosumab in breast and prostate cancer, and non-inferiority in other solid tumours. Osteonecrosis of the jaw is the most important side-effect of both drugs. A 2006 review notes that most available therapies for osteoporosis are inhibitors of bone resorption, but that the disease is heterogeneous and a more selective approach to therapy is needed. A 2014 review discusses the possibility of local bisphosphonate application to depress resorption at the bone-implant interface, noting that some work suggests local use is more effective for normalising remodelling and providing implant stability.
What is still missing is prospective data on whether local bisphosphonate delivery improves long-term implant survival in humans, and whether the bone mineral density gains seen with clodronic acid after fracture surgery translate into reduced reoperation rates or better functional outcomes. The orbital graft data show that even with good clinical results, more than half of reconstructed areas had substantial bone defects, and the long-term fate of those defects is unknown. No trial has yet combined local antiresorptive drugs with a stratified approach to the different pathogenetic factors in osteoporosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Plastic & Reconstructive Surgery · 2006 · 65 citations
Reconstruction of Internal Orbital Wall Fracture with Iliac Crest Free Bone Graft: Clinical, Computed Tomography, and Magnetic Resonance Imaging Follow-Up Study
AbstractBACKGROUND: The purpose of this study was to clinically and radiologically assess the outcome of internal orbital reconstruction with an iliac bone graft. METHODS: Twenty-four consecutive patients with unilateral orbital wall fractures were enrolled in this prospective study. A medial cortical wall from the anterior ilium was used for reconstruction. At each follow-up visit, globe posture, diplopia, and eye movements were assessed. Coronal and sagittal computed tomography and magnetic resonance imaging were used to observe graft posture, bone defects, and intraorbital soft-tissue changes. RESULTS: Most fractures (46 percent) were pure orbital floor fractures. The mean follow-up was 7.8 months. One patient with medial wall and floor fractures required reoperation because of insufficient bone graft. At the last follow-up, this was the only patient (4 percent) with both enophthalmos (2 mm) and hypophthalmos (3 mm). Five patients (21 percent) had hypophthalmos (> 1 mm) at the end of the study. Resorption and remodeling were detected in all grafts, but no grafts were totally resorbed. Sagittal or coronal bone graft postures were assessed as good in 18 orbits (75 percent). Bone defects (> 10 mm) at reconstructed areas were detected in 13 orbits (54 percent). Scar tissue was observed only in three reconstructed orbits (13 percent). Diplopia in central field of vision was registered in seven patients preoperatively but in none at the end of the study. CONCLUSIONS: The resorption rate was high, but most of it was advantageous remodeling. Overall outcome was good. Secondary operations led to poor outcomes. Thin computed tomography and magnetic resonance imaging sections (< or = 2 mm) are needed to evaluate accurately bone graft placement and posture and orbital volume.
New developments for treatment and prevention of bone metastases
AbstractPURPOSE OF REVIEW: To provide a critical review of recent trials of bone resorption inhibitory drugs (bisphosphonates and denosumab) for the treatment and the prevention of bone metastases in solid tumors. RECENT FINDINGS: The bisphosphonate zoledronic acid is now part of the standard treatment for metastatic bone disease. Comparative trials in this setting between zoledronic acid and denosumab have shown superior (in breast and in prostate cancer) or noninferior (in other solid tumors) skeletal-related event-prevention activity for denosumab. Osteonecrosis of the jaw is the most important side-effect of both compounds. Recent data also indicate the potential of zoledronic acid to reduce the recurrence rate in breast cancer. SUMMARY: Much progress has been accomplished for the treatment of tumor bone disease with bone resorption inhibitory drugs. Advances are now awaited in the setting of prevention of bone metastases.
Clinical Orthopaedics and Related Research · 2011 · 26 citations
The Effect of Antiresorptives on Bone Quality
AbstractBACKGROUND: Currently, antiresorptive therapy in the treatment and prevention of osteoporosis includes bisphosphonates, estrogen replacement, selective estrogen receptor modulators (raloxifene), and denosumab (a human antibody that inactivates RANKL). The original paradigm driving the development of antiresorptive therapy was that inhibition of bone resorption would allow bone formation to continue and correct the defect. However, it is now clear increases in bone density account for little of the antifracture effect of these treatments. QUESTIONS/PURPOSES: We examined the antifracture benefit of antiresorptives deriving from bone quality changes. METHODS: We searched the archive of nearly 30,000 articles accumulated over more than 40 years in our research center library using a software program (Refman™). Approximately 250 publications were identified in locating the 69 cited here. RESULTS: The findings document antiresorptive agents are not primarily anabolic. All cause a modest increase in bone density due to a reduction in the bone remodeling space; however, the majority of their efficacy is due to suppression of the primary cause of osteoporosis, ie, excessive bone remodeling not driven by mechanical need. All of them improve some element(s) of bone quality. CONCLUSIONS: Antiresorptive therapy reduces risk of fracture by improving bone quality through halting removal of bone tissue and the resultant destruction of microarchitecture of bone and, perhaps to some extent, by improving the intrinsic material properties of bone tissue. Information presented here may help clinicians to improve selection of patients for antiresorptive therapy by avoiding them in cases clearly not due to excessive bone remodeling.
Journal of Investigative Medicine · 2006 · 8 citations
Osteoporosis: How Should it be Treated?
AbstractOsteoporosis develops as a result of imbalance between bone resorption and bone formation. A number of effective and safe therapies for osteoporosis are currently available, most of which are inhibitors of bone resorption. However, because osteoporosis is a complex and heterogeneous disease with different pathogenetic factors, defining the role of the different factors in its development is important in formulating a more selective approach to therapy. This review discusses the advantages and disadvantages of the currently available agents used in the management of osteoporosis.
The effect of combined drug therapy in lateral fragility fractures of the femur: a prospective observational study.
AbstractOBJECTIVE: Due to a growing number of lateral fragility fractures, and their high economic and social impact, we evaluated the combined drug therapy effectiveness in lateral fragility femur fractures treated by intramedullary nailing surgery comparing the clinical and radiological results of two groups of patients. PATIENTS AND METHODS: From May 2019 to March 2020, we carried out a prospective observational study comparing the results of patients with femoral lateral fractures treated by the same intramedullary nail (PFNA Synthes®) using Clodronic acid and Vitamin D (study group, 25 patients) compared to patients with the same fractures treated with Vitamin D alone (control group, 25 patients). The evaluations were based on bone biochemical markers (serum calcium level, serum phosphate level, parathyroid hormone, Vitamin D, serum C-terminal telopeptide), Visual Analogic Scale and HHS (Harris Hip Score) score, and femur densitometric views. In order to evaluate the femur neck mineral bone density (BMD), two areas have been identified on the Anterior-Posterior view: the Region of Interest (ROI)1 (under the head screw) and the ROI2 (above the femoral screw). The BMD has been calculated using femur densitometric views at T0 (1st day post-surgery) and at T1 (12 months later). RESULTS: As far as the BMD average of ROI1 is concerned, we found a significant statistical increase at T1 in the study group (0.93±0.07 gr/cm2) vs. control group (0.88±0.08 gr/cm2), p=0.04. Both biochemical and densitometric values were statistically increased in the study group from T0 to T1 (p<0.05), while control group showed an improvement in the biochemical values only. CONCLUSIONS: Thanks to a one year follow-up, we are able to demonstrate that the administration of an adequate drug therapy after surgery can lead to a better control of the bone remodeling and reabsorption process.
Clinical Epidemiology and Global Health · 2024 · 1 citations · open access
Improving diagnosis of skeletal fluorosis in outpatient settings: A call for action
AbstractSkeletal fluorosis is a chronic metabolic bone osteopathy characterized by extensive bone fixation of fluoride. It is an endemic problem as a result of long-term exposure to high amounts of fluoride. It can lead to significant and crippling deformities, including kyphosis, restricted spinal and chest motion, and deformities of extraspinal joints, predisposing to hip osteoarthritis. Management of skeletal fluorosis generally focuses on symptomatic treatment. Preventive interventions are critical, including the provision of safe drinking water, defluoridation of water, and dietary intervention.
N N Priorov Journal of Traumatology and Orthopedics · 2014 · 0 citations · open access
Prospects for Local Application of Antiresorptive Drugs in Skeleton Bone Injuries and Diseases
AbstractIncrease in bone tissue resorption intensity on the border “metal - bone” as a compulsory component of remodeling in systemic osteoporosis or other metabolic osteopathies may result in poor surgical treatment results. Present review is dedicated to the analysis of available data on the possibility of local bisphosphonates application for the depression of resorption process in the zone of surgical intervention. In some works it is noted that just the local use of bisphosphonates is more effective for the normalization of remodeling and provision of biologic stability of the implants.
N N Priorov Journal of Traumatology and Orthopedics · 1996 · 0 citations · open access
Patho- morphologic Peculiarities of the Stages of Osteitis Deformans Develkopment (Paget’s Disease)
AbstractPathomorphologic examinations of the biopsy and operative specimens were performed in 39 patients with osteitis deformans who underwent surgery at the department of Bone Pathology in Adults (CITO) during the period fron 1958 to 1995. On the basis of the personal and literature data the authors underlined three stages of the osteitis deformans development that differed by the pathologic peculiarities and activity of the pathologic process: 1st stage - stage of osteolysis characterizing by marked bone resorption; 2nd stage - stage of remodelling characterizing by the combination of disturbance process and formation of new bone; 3rd stage - stage of the attenuation of pathologic process during which the resorption and new bone formation stopped. Application of drugs that inhibit bone tissue resorption is the most expedient in the 2nd and especially in the 1st stage of the disease.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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