Prevalence and determinants of radiological vertebral fractures in patients with Klinefelter syndrome

Abstract

Background Klinefelter syndrome (KS) may induce skeletal fragility, but the studies so far published on this topic were mainly focused on the evaluation of bone mineral density (BMD) and bone microstructure, whereas data on fracture risk are still lacking. Objective To evaluate the prevalence and determinants of vertebral fractures (VFs), that is, the hallmark of osteoporosis, in subjects with KS. Materials and methods Eighty‐seven patients with KS (median age 41 years, range 18‐64) were consecutively evaluated for radiological VFs (by quantitative morphometry) and lumbar spine and femoral neck BMD (by DXA). Fifty‐five patients with KS were also evaluated by the fracture risk assessment (FRAX) tool. Results Low BMD was found in 22/87 (25.3%) patients [12 with osteopenia, three with osteoporosis and seven with “low BMD per age” (subject < 50 years with Z‐score ≤−2.0 SD)] and VFs in 13/87 (14.9%) patients. In patients with VFs, the median spine deformity index was 2 (range 1‐9). Prevalence of VFs was similar between healthy and low‐BMD patients (15.9% vs 13.6%; P = .80). Noteworthy, patients with VFs had significantly higher age at diagnosis of KS as compared to patients who did not fracture (P = .039), without significant differences in age at the time of observation (P = .162), body mass index (P = .234), testosterone replacement therapy (P = .432), duration of testosterone therapy (P = .409), vitamin D therapy (P = 681), and serum testosterone levels (P = .338). Moreover, patients with VFs were more likely to complain back pain in comparison with those without VFs (33.3% vs 7.4%; P = .047). In 55 cases evaluated by the FRAX® tool, no significant differences in 10‐year risk of major fracture (P = .270) and hip fracture (P = .860) were found between fractured and non‐fractured patients. Conclusions This study provides first evidence that KS may be associated with risk of VFs in close relationship with delay in disease diagnosis but independently of BMD values and serum testosterone levels or testosterone therapy.

European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

“…Nevertheless, early diagnosis is quite rare but the increasing use of pre‐natal tests will increase the number of patients with KS being diagnosed. This should be an advantage for the patient and a great opportunity to prevent possible associated comorbidities later in life 213‐221 . However, the empirical evidence that early diagnosis with subsequent intervention improves long‐term adult outcomes is currently lacking 222‐238 .…”

“…This should be an advantage for the patient and a great opportunity to prevent possible associated comorbidities later in life. [213][214][215][216][217][218][219][220][221] However, the empirical evidence that early diagnosis with subsequent intervention improves long-term adult outcomes is currently lacking. [222][223][224][225][226][227][228][229][230][231][232][233][234][235][236][237][238] Physicians, especially paediatricians, should be aware of the relatively frequent incidence of KS and also the behavioural issues that might come with it.…”

Lessons of the month 3: Mosaic Klinefelter syndrome unveiled by acute vertebral fracture in a middle-aged man

“…1 In a study of 87 consecutive men with KS from tertiary endocrine centres, nearly one in five was found to have a vertebral fracture, and that was significantly associated with higher age at diagnosis, likely implying the greater risk of poor bone health with delayed diagnosis and treatment. 2 Another important finding was the lack of difference in Fracture Risk Assessment Tool (FRAX) score between those with fracture and without fracture, highlighting the inadequacy of traditional assessment method in determining fracture risk in hypogonadal men. 2 The theoretical application of the FRAX algorithm to this patient prior to his spine fracture would only yield 10-year probability of 1.8% for major osteoporotic fracture and 0.2% for hip fracture, well below the thresholds for intervention.…”

“…2 Another important finding was the lack of difference in Fracture Risk Assessment Tool (FRAX) score between those with fracture and without fracture, highlighting the inadequacy of traditional assessment method in determining fracture risk in hypogonadal men. 2 The theoretical application of the FRAX algorithm to this patient prior to his spine fracture would only yield 10-year probability of 1.8% for major osteoporotic fracture and 0.2% for hip fracture, well below the thresholds for intervention.…”

Strategies to improve early diagnosis of Klinefelter syndrome

“…For example, management of lifestyles, timely speech support, starting of testosterone treatment in cases of hypogonadism and fertility preservation might be optimally performed when diagnosis is done early and might be associated with better clinical progress of the syndrome and its possible clinical sequelae. For example, a recent study showed that the rate of osteoporosis and fractures in adult men with Klinefelter syndrome is correlated to age at diagnosis [9].…”