To our knowledge, this is the first study to illustrate the bone loss, microarchitectural decay and increased fracture risk in BMT recipients over an extended follow-up period. In this group, there was rapid, significant bone loss post BMT, most pronounced in the first year following transplant, mirroring the timeline of glucocorticoid-induced osteoporosis [8]. Notably however, bone loss was greatest at the femoral neck, while glucocorticoid-induced osteoporosis predominantly affects the spine [9]. This is consistent with previous studies [3]. Decay in bone microarchitecture was also noted as evidenced by the decline in TBS post BMT. TBS decline was independent of T-score decline, as has previously been demonstrated in renal transplant recipients [10]; TBS and aBMD are therefore complementary methods for assessing bone quality.

Similar to previous studies of BMT recipients [11, 12], the femoral neck and hip sites had greater annualised bone loss than the lumbar spine. This may be partially explained by immobility-related bone loss, where demineralisation of the weight-bearing skeleton including the femur and tibia lead to reduced bone density and increased fracture risk at these sites [13, 14]. Exercise has been shown to improve function, quality of life and length of stay in BMT recipients [15]. In our study, BMT recipients were admitted for a median of one month in the year after transplant, however frequency of admission did not correlate with annualised decline in aBMD. Research into other pathophysiological mechanisms is warranted, including investigation of vitamin D status post BMT. Some studies have suggested vitamin D deficiency may be prevalent in BMT recipients [16], although this was not the case in our cohort.

This deterioration in bone health translates to an increased fracture risk. Of concern, these patients are fracturing despite relatively preserved aBMD and TBS at the time of first DXA scan. We recorded 19 fractures over 3884 person years of follow-up, which equates to a 5.3% probability of osteoporotic fracture over the median 11-year study period. Some studies have reported an even greater risk, with up to 8–10.6% of BMT recipients experiencing fragility fractures [17, 18]. This high probability of fracture in the BMT subpopulation is greater than that estimated by conventional fracture probability calculators including FRAX®, which do not include BMT as a risk factor. Glucocorticoids have been shown to increase fracture risk independent of aBMD [19], and similarly our study found fracture incidence was independent of annualised aBMD decline.

TBS is a novel and useful adjunct that can assist clinicians in predicting future fractures. FRAX®-TBS predicted a higher (although not significant) probability of fracture compared to FRAX® alone. TBS is known to improve fracture risk assessment in glucocorticoid-induced osteoporosis and, given that this is a factor in BMT recipients, further supports TBS utility in the BMT population [20].

There are few studies of TBS in BMT patients and they have contrasting findings. Pawlowska et al. [21] evaluated 137 patients to find that TBS declined significantly in women and patients treated with glucocorticoids. Conversely in 68 patients, Lim et al. [3] found no significant change in TBS from baseline to 12 months and from 12 to 24 months, although the sample size was small. Further study of TBS in the BMT population could assess its utility in guiding earlier appropriate antiresorptive treatment. Currently, there are no accepted thresholds for TBS alone to prompt antiresorptive therapy, although this may change in the future. Instead, its present utility is in augmenting fracture probability estimates, e.g. FRAX®-TBS, or qualitatively when considered in conjunction with aBMD.

Our study is limited by being a retrospective, single-centre cohort study. There were also limited glucocorticoid exposure data available, which may have contributed to an underestimate of FRAX fracture risk. The relatively younger age of individuals post BMT may have also contributed to an underestimated fracture risk, with younger BMT recipients less likely to fracture than older recipients [18]. The study is strengthened by a relatively large sample size with substantive longitudinal follow-up and the ability to assess fracture occurrence. While there were only 47 patients with sequential TBS available in our study, there are limited data on TBS in the BMT population and thus this represents a relatively sizeable population. There were a small number of patients who fractured, which may limit comparisons between the group of patients who did and did not fracture. For patients who did not respond to the survey, fracture data were collected from the medical record and this method may have missed some fractures that occurred in the community. However, this study provides a fresh perspective on fracture probability and TBS utility in this population that may be confirmed with future research endeavours.

Patients post BMT are vulnerable and experience long-term health consequences post-transplant. This includes a high risk of declining bone health and fracture, which is multifactorial. Recognising declining bone health early is paramount as it allows earlier institution of effective and well-tolerated antiresorptive therapies where appropriate. The FRAX algorithm was derived from patients older than forty years of age, and is therefore less applicable to BMT patients who are younger than other solid organ transplantation cohorts such as kidney transplant recipients [22].

Unlike solid organ transplant recipients who are often on lifelong glucocorticoids, BMT subjects are weaned off immunosuppressants. Therefore, fracture calculators underestimate absolute fracture risk because they do not register BMT recipients with additional risk factors either via prolonged high-dose glucocorticoids use or the presence of secondary osteoporosis with chronic conditions such as type 1 diabetes or chronic liver disease. An additional adjustment factoring BMT into fracture probability calculators may improve bone health assessment in the future. We propose a factor adjustment by at least 100–200% based on the 5.3% fracture prevalence in our study compared to the 2.69% FRAX estimate although this may be an underestimate due to limited glucocorticoid data. This may encourage earlier intervention with antiresorptive therapy where appropriate, thereby minimising preventable fractures.

The current recommendation post BMT is to assess aBMD using DXA at baseline and within one year post-transplant or at 3 months if there has been exposure to high-dose corticosteroids early post-transplant [6, 23]. Newer guidelines recommend antiresorptive therapy if DXA T-score < 1.5 [24]. The guidelines in solid organ recipients recommend antiresorptive therapy in those with osteopenic T-score to offset the rapid bone loss immediately post-transplantation. Our study demonstrated rapid aBMD decline in the first year post BMT independent of TBS decline, therefore we recommend a DXA scan with TBS at baseline and within one year post BMT with subsequent DXA scans guided by the clinical picture.

Akin to the current literature, prophylactic antiresorptive therapy was not administered to many patients with an indication for treatment. Eighty-four patients had clinically-defined osteoporosis, either having T-scores in the osteoporotic range or a low-trauma fracture plus osteopenic aBMD, providing an indication for antiresorptive therapy. Seventeen of these patients received antiresorptive, corresponding with a 20% treatment rate. In the BMT population, multidisciplinary collaboration and further research may improve fracture risk calculation and earlier antiresorptive therapy where appropriate.