Case Report: Longitudinal skeletal outcomes during intravenous bisphosphonate therapy in two siblings with SGMS2-associated osteoporosis and calvarial doughnut lesions

Background Pathogenic SGMS2 variants are a rare cause of monogenic skeletal fragility, and longitudinal treatment data in affected children are limited. Case description We report two sisters carrying the recurrent heterozygous SGMS2 c.148C>T, p.(Arg50Ter) variant who presented with calvarial doughnut lesions, markedly reduced lumbar spine (LS) and total body less head (TBLH) bone mineral density (BMD), and multiple vertebral compression fractures despite no preceding pattern of recurrent peripheral low-trauma fractures. Both received nine cycles of intravenous pamidronate followed by three cycles of zoledronic acid; the switch reflected temporary pamidronate unavailability. During follow-up, LS BMD Z-scores increased from -3.3 to -0.6 and from -3.1 to -0.5, while TBLH BMD Z-scores increased from -2.7 to -0.9 and from -2.3 to -0.7 in Patients 1 and 2, respectively. Neither patient sustained a new low-trauma fracture. Vertebral morphology evolved differently, with reshaping in Patient 1 but persistent vertebral height reduction in Patient 2. Celiac disease was diagnosed in both sisters during treatment, and pubertal development differed between them. Conclusion These observations show substantial longitudinal increases in BMD Z-scores and the absence of new low-trauma fractures during intravenous bisphosphonate therapy, while vertebral morphological outcomes differed between the siblings. Growth, pubertal maturation, and treatment of concomitant celiac disease may also have influenced bone accrual; longitudinal assessment should therefore integrate fractures, vertebral morphology, growth, maturation, and DXA.