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Clinical Trials/NCT03175874
NCT03175874CompletedNot Applicable

AVP Study: Autophagy and Pathological Aging Human Study in Osteoporosis With or Without Dementia of Alzheimer's Type

Centre Hospitalier Universitaire de Nice1 site in 1 country82 target enrollmentStarted: December 20, 2017Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Not Applicable
Status
Completed
Enrollment
82
Locations
1
Primary Endpoint
Quantification of autophagy

Study Overview

Brief Summary

Autophagy is recognized as a central mechanism for the regulation of aging. . Osteoporosis (OA) and Alzheimer's disease (AD) are two forms of pathological aging, sometimes entangled, including an over-risk of OP in AD and degradation of cognitive functions after OP fracture, but the link between These two pathologies remain poorly understood.

The aim of this prospective pilot study is to evaluate the level of autophagy of osteocytes (OST) in postmenopausal women with OP and to explore the hypothesis that the defect of autophagy is one of the physiopathological links of the OP During the MA

Detailed Description

Autophagy is a ubiquitous cellular mechanism that degrades and recycles toxic waste from cells. It is recognized as a central mechanism for the regulation of aging. Osteoporosis (OA) and Alzheimer's disease (AD) are two forms of pathological aging, sometimes entangled, including an over-risk of OP in AD and degradation of cognitive functions after OP fracture, but the link between These two pathologies remain poorly understood. In Alzheimer's disease (AD), a deficiency of autophagy is found both clinically and fundamentally. In animal studies, animal studies have shown that autophagy is involved in the differentiation, function and survival of bone cells, decreases with age and that a defect in autophagy is accompanied by a decrease in The bone mass. To date, we do not have human data on the autophagic capacities of bone cells in OP and AD.

The aim of this prospective pilot study is to evaluate the level of autophagy of osteocytes (OST) in postmenopausal women with OP and to investigate the hypothesis that the defect of autophagy is one of the physiopathological links of the OP During the MA.

The main objective is to determine, in two subgroups with or without Alzheimer's disease, whether there is an association between bone status and the level of autophagy of OST in postmenopausal women (OP versus non-OP)

Secondary objectives are to determine whether there is an association between the level of autophagy of the OST and the bone parameters (bone mineral density, serum vitamin D) and to compare in OP women the level of autophagy of the OST Of AM patients vs no MA.

Study population: Postmenopausal women over the age of 65 benefiting from the implantation of a hip prosthesis: 30 with an OP fracture of the femoral neck (15 non-MA and 15 MA, the cognitive status being determined by MMSE And IADL 1 month after the fracture) and 30 controls performed for osteoarthritis, free from OP (antecedents + bone mineral density) and MA (MMSE and IADL).

Study Design

Study Type
Interventional
Allocation
Non Randomized
Intervention Model
Single Group
Primary Purpose
Basic Science
Masking
None

Eligibility Criteria

Ages
65 Years to — (Older Adult)
Sex
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • •Inclusion criteria for both groups:
  • •Women > 65 y: 2 groups
  • •Inclusion criteria for Osteoporosis group (Alzheimer and non-Alzheimer):
  • •Osteoporotic femoral neck fracture requiring hip remplacement and fullfilling WHO definition of osteoporosis. Without any cognitive impairment for the first subgroup (MMSE > 26 and normal IADL) and with a final diagnosis of alzheimer disease in the other subgroup (DSM-IV-TR)
  • •Inclusion criteria for Control group:
  • •Non osteoporotic (no fragility fracture (clinical or on VFA) and bone mineral density T-score > 2.5 SD at all sites)
  • •No cognitive impairment (MMSE > 26 and normal IADL)

Exclusion Criteria

  • •Non-Inclusion Criteria for both groups:
  • •Other pathologies associated with autophagy: Parkinson's disease, Crohn's disease, cancers, myopathies, type 2 diabetes
  • •Méd Medications interfering with autophagy: current corticosteroids, parathyroid hormone, estrogen, chloroquine, hydroxychloroquine, lithium, metformin, bisphosphonates,
  • •Dementia of non-Alzheimer type

Arms & Interventions

osteoporosis and alzheimer

Other

patient with osteoporosis and alzheimer hospitalized for total hip prosthesis.

Intervention: Hip bone sampling (Procedure)

osteoporosis without alzheimer

Other

Patient with osteoporosis without alzheimer hospitalized for total hip prosthesis.

Intervention: Hip bone sampling (Procedure)

Patient with arthrosis without alzheimer

Other

Patient with arthrosis without alzheimer hospitalized for total hip prosthesis.

Intervention: Hip bone sampling (Procedure)

Outcomes

Primary Outcomes

Quantification of autophagy

Time Frame: at inclusion

Quantification of autophagy (LC3II and SQSTM1 / p62) by Western blotting of purified OST proteins from a bone sample from resected femoral heads

Secondary Outcomes

  • 25 OH vitamin D (ng/ml).(at inclusion)
  • Bone mineral density(at inclusion)

Investigators

Sponsor Class
Other
Responsible Party
Sponsor

Study Sites (1)

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