12 Chapter 1 General introduction Benign bone and joint disease: scope of this thesis Benign bone and joint diseases are a heterogeneous range of diseases, including degenerative, infectious and inflammatory, metabolic, congenital, traumatic, and iatrogenic origin. The general practitioner, orthopedic surgeon, trauma surgeon, endocrinologist, rheumatologist, radiologist and nuclear medicine physician, have an interest in one or more of these pathologies. Besides history taking and physical examination, imaging has acquired a central role in the diagnosis and follow-up of many of these diseases. Osteoarthritis is the most prevalent bone disease and may affect any joint in the body. Knee degenerative joint disease is responsible for almost 80% of the burden of osteoarthritis worldwide [1]. Although age is an important contributing risk factor for osteoarthritis, not only elderly are affected by degenerative joint disease. For example, tarsal coalition is a common congenital cause of foot pain in adolescents due to an abnormal connection of two or more of the bones linking the hind- and midfoot. It may cause pain in the affected joint in adolescents and young adults, as well as secondary osteoarthritis in adjacent joints before the fourth decade. Fibrous Dysplasia / McCune Albright Syndrome (FD/MAS), in contrast, is a rare benign metabolic bone diseases which may affect one or multiple bones anywhere in the skeleton, leading to a broad variety of clinical manifestations. This thesis studied the (potential) role of specific molecular and multimodality imaging in three groups of patients with benign bone and joint disease: 1. severe osteoarthritis of selected joints of the extremities (i.e., knee, hand and wrist) in evaluation for unexplained pain after surgery 2. tarsal coalition at primary diagnosis after plain radiographs and during follow-up after surgery 3. FD/MAS before and after treatment with bone remodeling therapy Osteoarthritis, extent of the problem Bone and joint diseases lead to high burden on individuals, health and social-care systems and its negative effect on disability-adjusted life-years (DALY’s) is growing faster than most non-communicable diseases [2, 3]. To illustrate the impact of bone and joint diseases, in the Netherlands, in 2020, an estimated 40,900 people were newly diagnosed with osteoarthritis of the knee by the general practitioner (15,400 men, 25,500 women) and in total over 746,000 Dutch citizens had knee osteoarthritis, making it the most prevalent form of osteoarthritis [4]. For our country, in 2019 the