Table 3.

Risk factors (RF) for osteoporotic fracture in patients with Helicobacter pylori infection.

General/Common RF	HPI-Induced Diseases and Disorders
Advanced age	Anemia, iron deficiency
Menopause/male hypogonadism	Vitamin B12 deficiency
Body mass loss	Immune thrombocytopenia
Low BMD	Chronic/atrophic gastritis
Previous fragility fracture	PUD
History of falls	Gastric malignancy
Family history of OP/OFs	HPI- associated chronic diseases and disorders
Ethnicity (Caucasian and Asian vs. black populations)	Cardiovascular diseases (CAD, CHF, AF, hypertension)
Impaired balance, gait and mobility, need of assistive device *	Hemodynamic instability (orthostatic and/or postprandial hypotension, dizziness) #
Low physical activity/immobilization	Cerebrovascular diseases (stroke, TIA)
Low body mass index	Neurodegenerative diseases (dementia, Parkinson’s disease)
Hemodynamic instability (orthostatic and/or postprandial hypotension, dizziness) #	COPD
Visual impairment	CKD
Vitamin D deficiency/insufficiency	Diabetes mellitus
Vitamin K deficiency	Metabolic syndrome
Hyperparathyroidism	CLD
Urinary incontinence #	Depression, anxiety
Low calcium intake	Rheumatologic diseases
Fear of falling #	Eye diseases (open-angle glaucoma, neuromyelitis optica)
Prolonged use of certain medications	Gut dysbiosis
Corticosteroids, antidepressants (especially, SSRIs, SSNRIs), opioids, anxiolytics, hypnotics, sedatives (benzodiazepines), antiparkinsonian (dopaminergic) medications, antipsychotics, antiepileptics, glitazones, antiarrhythmics, PPIs, thyroxine, aromatase inhibitors, gonadotropin releasing hormone antagonists, immunosuppressive agents, polypharmacy	Malignant tumors (breast, lung, colorectal, prostate cancers)
Environmental, lifestyle and socio-economic RF
Cigarette smoking, excess alcohol consumption, diet, urbanization, poor sanitation conditions, air pollution.

Abbreviations: AF, atrial fibrillation; CAD, coronary artery disease; CHF, congestive heart failure; CKD, chronic kidney disease; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; PPI, proton pump inhibitor; PUD, peptic ulcer disease; SSRI, selective serotonin reuptake inhibitors; SSNRI, selective serotonin-norepinephrine reuptake inhibitors; TIA, transient ischemic attack; # Risk factor for falls (not for OP); * although need for an assistive device indicates presence of conditions predisposing to falls, its appropriate use may actually decrease fall risk. Notes: Recent genetic studies have challenged some long-assumed risk factors for OP/OF. Mendelian randomization analyses identified BMD [413,635,636,637], serum estradiol concentrations (in men) [638] and cigarette smoking [639] as causal risk factors for OP/OFs, whereas genetic predisposition to lower levels of vitamin D and milk calcium intake [635,636,639,640], serum testosterone [638] and inflammation markers [641,642], as well as early menopause; late puberty, chronic (including CVD, DM and IBD) [413,414,643] and neuropsychiatric diseases (Alzheimer’s disease, schizophrenia and bipolar disorder) [644], alcohol consumption [645] and alcohol dependence [639] did not show causal effects on BMD and fracture risk. The genetic studies overcome many limitations of the previous observational studies but also contain potential bias; “the Mendelian randomization study design cannot be used to assess whether complications or treatment of those diseases influence fracture risk” [636].