Reversibility in male idiopathic osteoporosis possible

Summary: A 44-year-old athletic man presented in 2009 with severe low back pain. Dual-energy x-ray absorptiometry revealed severe osteoporosis; serum testosterone was 189 ng/dL while serum estradiol (E2) measured by liquid chromatography/mass spectrometry was 8 pg/mL. DNA was extracted and sequenced from a blood sample from the patient since his maternal first cousin also had low bone mass and both patients were screened for aromatase dysfunction by PCR analysis for the CYP19A1 gene, which encodes aromatase. No known pathologic mutations were observed in the coding exons, but novel single nucleotide polymorphisms were detected both in the proband and in his cousin. Treatment with topical testosterone started in August 2010. Over the next 8 years, testosterone dosage was varied and switched from topical gel to injections and maintained on depo-injections of testosterone at about 60 mg once per week. Re-examination in March 2012 included a brain MRI to exclude pituitary lesions; hyperparathyroidism was ruled out (normal serum parathyroid hormone, calcium, and calcium to phosphorous ratio) and celiac disease was excluded (negative transglutaminase antibodies). Follow-up in October 2018 showed improved bone mineral density of the lumbar spine by 29% and of the left femoral hip by 15% compared to baseline measurements. This reveals the importance of measuring serum E2 for making the correct diagnosis, as well as for monitoring a therapeutic effect. Herein, we propose treatment of male osteoporosis where serum E2 levels are below about 20 pg/mL with testosterone to reverse osteoporosis. Learning points: Estrogen deficiency in the diagnosis of male idiopathic osteoporosis. Importance of serum estradiol in male osteoporosis. Role of polymorphisms in aromatase gene on bone health. Reversal of osteoporosis. Tailored testosterone treatment for bone health

Using INTERCheck® to Evaluate the Incidence of Adverse Events and Drug–Drug Interactions in Out- and Inpatients Exposed to Polypharmacy

Background: Polypharmacy exposes patients with comorbidities (particularly elderly patients) to an increased risk of drug-specific adverse events and drug–drug interactions. These adverse events could be avoided with the use of a computerized prescription support system in the primary care setting. The INTERCheck® software is a prescription support system developed with the aim of balancing the risks and benefits of polytherapy and examining drug–drug interactions. Objectives: This observational study used the INTERCheck® software to evaluate the incidence of adverse events and of drug–drug interactions in outpatients and inpatients receiving multiple medications. Methods: Patients were randomly enrolled from the outpatient department (n = 98) and internal medicine ward (n = 46) of S. Andrea Hospital of Rome. Polypharmacological treatment was analyzed using INTERCheck® software, and the prevalence of risk indicators and adverse events was compared between the two groups. Results: Polypharmacy (use of five or more drugs) applied to all except three cases among outpatients and one case among inpatients. A significant positive correlation was found between the number of medications and the INTERCheck® score (ρ = 0.67; p < 0.000001), and a significant negative correlation was found between the drug-related anticholinergic burden and cognitive impairment (r = − 0.30 p = 0.01). Based on the INTERCheck® analysis, inpatients had a higher score for class D (contraindicated drug combination should be avoided) than did outpatients (p = 0.01). The potential class D drug–drug interactions were associated with adverse events that caused hospitalization (χ2 = 7.428, p = 0.01). Conclusions: INTERCheck® analysis indicated that inpatients had a high risk of drug–drug interactions and a high percentage of related adverse drug events. Further prospective studies are necessary to evaluate whether the INTERCheck® software may help reduce polypharmacy-related adverse events when used in a primary care setting and thus potentially avoid related hospitalization and severe complications such as physical and cognitive decline