Citation: Zaia, A.; Maponi, P.; Sallei, M.; Galeazzi, R.; Scendoni, P. Measuring Drug Therapy Effect on Osteoporotic Fracture Risk by Trabecular Bone Lacunarity: The LOTO Study. Biomedicines 2023, 11, 781. https://doi.org/10.3390/ biomedicines11030781 Academic Editor: Vasileios Tzounakas Received: 10 February 2023 Revised: 28 February 2023 Accepted: 2 March 2023 Published: 4 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). biomedicines Article Measuring Drug Therapy Effect on Osteoporotic Fracture Risk by Trabecular Bone Lacunarity: The LOTO Study Annamaria Zaia 1, * , Pierluigi Maponi 2 , Manuela Sallei 3 , Roberta Galeazzi 4 and Pietro Scendoni 5 1 Centre of Innovative Models and Technology for Ageing Care, Scientific Direction, IRCCS INRCA, 60121 Ancona, Italy 2 School of Science and Technology, University of Camerino, 62032 Camerino, Italy 3 Medical Imaging Division, Geriatric Hospital, IRCCS INRCA, 60121 Ancona, Italy 4 Analysis Laboratory, Geriatric Hospital, IRCCS INRCA, 60121 Ancona, Italy 5 Rheumatology Division, Geriatric Hospital, IRCCS INRCA, 63900 Fermo, Italy * Correspondence: a.zaia@inrca.it Abstract: An MRI method providing one parameter (TBLβ: trabecular-bone-lacunarity-parameter-β) that is sensitive to trabecular bone architecture (TBA) changes with aging and osteoporosis is under study as a new tool in the early diagnosis of bone fragility fracture. A cross-sectional and prospective observational study (LOTO: Lacunarity Of Trabecular bone in Osteoporosis) on over-50s women, at risk for bone fragility fracture, was designed to validate the method. From the baseline data, we observed that in women with prevalent vertebral fractures (VF+), TBA was differently characterized by TBLβ when osteoporosis treatment is considered. Here we verify the potential of TBLβ as an index of osteoporosis treatment efficacy. Untreated (N = 156) and treated (N = 123) women were considered to assess differences in TBLβ related to osteoporosis treatment. Prevalent VFs were found in 31% of subjects, 63% of which were under osteoporosis medications. The results show that TBLβ discriminates between VF+ and VF- patients (p = 0.004). This result is mostly stressed in untreated subjects. Treatment, drug therapy in particular (89% Bisphosphonates), significantly counteracts the difference between VF+ and VF- within and between groups: TBLβ values in treated patients are comparable to untreated VF- and statistically higher than untreated VF+ (p = 0.014) ones. These results highlight the potential role of TBLβ as an index of treatment efficacy. Keywords: osteoporosis; fracture risk; osteoporosis treatment; vitamin D; drug therapy; bispho- sphonates; trabecular bone microarchitecture; magnetic resonance imaging; fractal analysis; fractal lacunarity 1. Introduction The World Health Organization (WHO) defines osteoporosis as a systemic skeleton disease characterized by bone mass loss and microarchitectural deterioration of bone tissue that induces bone fragility and increased susceptibility to fractures [1]. Bone fragility fractures account for increased morbidity and mortality in the geri- atric population and perimenopausal women show the highest risk of early osteoporosis onset [2–4]. In fact, postmenopausal osteoporosis is peculiar to 50–65-year-old women be- cause of the fast resorption of trabecular bone, which is associated with estrogen deficiency. The pattern of bone fragility fracture in postmenopausal osteoporosis primarily involves vertebras, whereas senile osteoporosis, affecting over 65-year-old subjects, is mainly charac- terized by fractures at the hip and femur, when deterioration of bone tissue also involves the cortical bone [5]. It should be pointed out that bone deterioration is a silent process and osteoporosis is often diagnosed after a painful bone fracture occurs [4]. It is known that the first fracture event worsens the risk of new fractures and speeds up their onset. In addition, vertebral fractures (VFs) are generally painful, accompanied by a loss of function, and can even Biomedicines 2023, 11, 781. https://doi.org/10.3390/biomedicines11030781 https://www.mdpi.com/journal/biomedicines