Biology of Blood and Marrow Transplantation
Volume 16, Issue 8 , Pages 1130-1137, August 2010

Accelerated Bone Mineral Density Loss Occurs with Similar Incidence and Severity, But with Different Risk Factors, after Autologous versus Allogeneic Hematopoietic Cell Transplantation

  • Song Yao

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Shannon L. Smiley

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Kathleen West

      Affiliations

    • Department of Pharmacy, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Dominick Lamonica

      Affiliations

    • Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Minoo Battiwalla

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Philip L. McCarthy Jr.

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Theresa Hahn

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • Corresponding Author InformationCorrespondence and reprint requests: Theresa Hahn, PhD, Department of Medicine, BMT Program, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263.

Received 13 January 2010; accepted 19 February 2010. published online 25 February 2010.

Article Outline

Bone mineral density (BMD) loss occurs commonly in patients after allogeneic hematopoietic cell transplantation (HCT), primarily because of steroid use, but little is known about BMD change post-autologous HCT. In a prospective study of 206 consecutive first HCT patients, we measured acute BMD change at the lumbar spine and dual femur between baseline and day +100, and evaluated risk factors for bone loss. Accelerated BMD loss in this 4-month period occurred after both autologous and allogeneic HCT with similar severity (median, 0.03 g/cm2 versus 0.03 g/cm2 at the spine; 0.03 g/cm2 versus 0.05 g/cm2 at the femur, respectively). This is equivalent to 7 to 17 years' worth of bone loss by aging. Risk factors for BMD loss were different between autologous and allogeneic HCT patients: lymphoma was associated with greater bone loss after autologous HCT than myeloma, whereas higher steroid dose was the most significant risk factor after allogeneic HCT. Multivariable risk models explained 11% to 30% of the variation in HCT-related BMD change. Surprisingly, BMD loss post-autologous HCT occurred with similar incidence and severity to allogeneic HCT, even in the absence of steroid use. Evaluation of clinical strategies to prevent and reverse HCT-related BMD loss is necessary in both autologous and allogeneic HCT patients.

Key Words: Bone mineral density, Autologous HCT, Allogeneic HCT, Risk factors

 

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Introduction 

Hematopoietic cell transplantation (HCT) cures patients with otherwise fatal hematologic diseases [1], making quality of life among survivors an increasingly important issue to be addressed. Accelerated bone mineral density (BMD) loss is a common complication after both solid organ and stem cell transplantation, characterized by rapid bone loss, which persists for many years 2, 3, 4, 5, 6, 7, 8. This accelerated premature bone aging exponentially increases the risk of fractures, where a 10% to 15% BMD loss approximately doubles the fracture risk 9, 10.

Our previous retrospective study demonstrated that BMD loss occurs frequently after allogeneic HCT, even in the absence of steroid exposure, and that antiresorptive bisphosphonate treatment was effective in reversing the bone loss in osteoporotic patients [11]. Several other studies have also demonstrated efficacy at reversing BMD loss post-HCT with bisphosphonates 12, 13, 14, 15, 16, 17; however, vitamin D with or without calcium supplementation, and hormone replacement therapy have failed to prevent or reverse bone loss 12, 14, 18, 19.

Although risk factors for BMD loss after allogeneic HCT with myeloablative (MA) conditioning have been described 6, 7, there are no data on the incidence and severity of BMD loss after allogeneic HCT with NMA or reduced-intensity conditioning (RIC) regimens. Moreover, for patients undergoing autologous HCT, BMD change has only been reported in small series with inconsistent findings. In a retrospective cross-sectional study of 68 autologous HCT patients, 28% had osteopenia or osteoporosis at the spine and 54% at the femur a median of 4.2 years after transplant [20]. Another study of 10 autologous HCT patients followed for 12 months after transplant showed a nonsignificant reduction of BMD at the spine (−1.1%) but an increase at the femur (1.5%) [21]. These results conflict with a prospective study including both autologous and allogeneic HCT patients, which reported a nonsignificant loss at the spine (−2.4%) and a significant BMD loss at the femur (−3.8%) at 3 months after transplant [22].

In the present study, we sought to compare the incidence, severity, and risk factors for BMD loss between autologous and allogeneic HCT patients. Steroid exposure is infrequent after autologous HCT, but shows a strong correlation with BMD loss after allogeneic HCT; therefore, we hypothesized that incidence and risk factors for accelerated BMD may differ between these 2 HCT patient groups.

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Materials and Methods 

Patient Population 

Beginning in January 2006 as part of routine clinical care, dual-energy X-ray absorptiometry (DXA) scans and serum levels of 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), and calcium were prospectively measured at baseline and day +100 after transplantation in patients undergoing autologous and allogeneic HCT in the Blood and Marrow Transplantation Program at Roswell Park Cancer Institute (RPCI). No vitamin D or routine calcium supplementation was given during this time period. Calcium replacement was only administered for critical values of ionized calcium <1.19 mmol/L. By January 2009, a total of 206 adult (≥18 years) patients underwent their first HCT, 197 (96%) of whom had a baseline DXA scan a median 20 days pre-HCT. The most common reason for not obtaining a baseline DXA was because of the patient's weight exceeding the maximum limit of the DXA scanner (300 pounds). Of those with a baseline DXA scan, 146 (74%) had a second DXA scan a median 98 days post-HCT. The reasons for not obtaining a follow-up DXA scan were because of early death or relapsed disease (N = 37) or unstable medical status (N = 14). This study was reviewed and approved as a nontherapeutic protocol by the institutional review board (IRB) at RPCI. All data presentations have been deidentified.

Autologous High-Dose Therapy and Allogeneic Conditioning Regimens 

High-dose therapy regimens before autologous HCT varied by underlying disease, age and performance status. In the 102 autologous HCT patients with a baseline DXA scan, these regimens included: cyclophosphamide (C) + carmustine (B) + etoposide (V) (N = 37), 120-200 mg/m2 melphalan (M) (n = 32), busulfan (Bu) + C (n = 26), or total body irradiation (TBI) based (N = 7). Conditioning regimens before allogeneic HCT also varied by underlying disease, age, and performance status. MA regimens in the 95 allogeneic HCT patients with a baseline DXA scan included: C + 1200-1350 cGy TBI (n = 16), Bu + C (n = 12) or V + TBI (n = 1). RIC regimens included: fludarabine (Flu) + M (n = 57) or Flu + C ± other (n = 9).

Graft-versus-Host Disease (GVHD) Prophylaxis and Treatment 

Prophylaxis for GVHD varied by age, underlying disease risk, donor relation, stem cell source, and protocol. In the 95 allogeneic HCT patients who had a baseline DXA scan, these regimens included: tacrolimus (FK) + methotrexate (MTX) + mycophenolate mofetil (MMF) (N = 38), FK + MMF (N = 29), FK + MTX (n = 22), or other (N = 6). Tacrolimus levels were checked twice weekly to maintain levels between 5 and 15 ng/mL. It was initially given intravenously and converted to oral once patients tolerated oral medication, and was tapered in the absence of GVHD beginning at day +30 for high-risk disease or day +100 for low-risk disease. MTX was dosed at 2.5, 5, or 10 mg/m2 and given on days +1, +3, +6 ± day +11, depending on age, donor relation, stem cell source, and underlying disease risk.

First-line treatment for acute GVHD (aGVHD) was escalation of calcineurin inhibitor to the maximum dose tolerated by renal function and initiation of methylprednisolone 2 mg/kg for 3 days. If there is no response after 72 hours of corticosteroids, additional treatment was initiated either through enrollment on a steroid-refractory GVHD protocol or per the program's standard operating procedure for GVHD treatment.

BMD Measurement 

BMD at the lumbar spine (average of L2, L3, and L4) and at the dual femur (average of 2 entire femora) was quantified by DXA scans using a single GE® Lunar Prodigy™ scanner (GE Medical Systems, Piscataway, NJ). The coefficient of variance was 0.94% at the spine and 0.76% at the femur. To adjust for random errors with repeated measurements, we defined a “significant” change of BMD according to the criteria recommended by the International Society of Clinical Densitometry that the least significant change between 2 consecutive DXA scans must exceed 2.77 times the coefficient of variance [23]. This translates to a minimum change of 2.6% at the spine and 2.1% at the femur in our study. In addition, we also annualized BMD loss rates in our patients and compared those to the expected normal rates in the general population between 20 and 89 years of age: 0.1% at the spine and 0.3% at the femur in males and 0.4% at the spine and 0.6% at the femur in females [24]. T-score and Z-score were reported and osteopenia and osteoporosis was classified by T-score following the WHO criteria [25].

Statistical Analyses 

Serum levels of calcium were adjusted for albumin [26] and the cumulative steroid dose received between the 2 DXA scans was calculated as prednisone equivalents [27]. Due to variations in the length of time between 2 DXA scans, all BMD changes were standardized to 100 days. Data in autologous and allogeneic HCT patients were analyzed separately. BMD was analyzed as a continuous variable. The change in BMD was calculated and analyzed in all statistical tests as (post-HCT BMD − baseline BMD), so BMD loss resulted in a negative value and a gain in BMD resulted in a positive value. For clarity, we present the absolute value of the change in BMD in the tables and text and indicate whether this was a loss or gain in BMD.

Nonparametric Wilcoxon rank test and McNemar's exact test were used for comparisons of continuous and categoric variables between 2 DXA scans or other univariate comparisons where appropriate. The Pearson correlation test was used for linear correlations. For multivariable analyses, dummy variables were created for categorical variables, and linear regression models were fitted. Factors with a P-value ≤.10 in the univariate analyses were entered and evaluated by backward elimination in the multivariable models, and those with a P-value <.05 were retained in the final models. Coefficients of determination (R2) were adjusted by the degrees of freedom and used as a measure of the proportion of variance in BMD change that can be explained by the clinical risk factors. All analyses were 2-sided with type I error of 0.05 and performed using SAS 9.1 (SAS Institute, Cary, NC).

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Results 

Of 197 patients who had a baseline DXA scan, 102 (52%) were autologous and 95 (48%) were allogeneic HCT patients (see Table 1). Plots of the change in T-score between baseline and post-HCT DXA scans are shown in Figure 1. At baseline, few patients had osteoporosis (4% at the spine and 3% at the femur) and a number of patients had osteopenia (17% at the spine and 20% at the femur). After transplantation, BMD in most patients remained in the normal range; however, the majority of patients experienced a significant BMD loss at the spine (54%) or femur (79%). The rate of osteoporosis remained low (5% at the spine and 6% at the femur), but the rate of osteopenia was significantly increased (26% at the spine and 28% at the femur, P < .001).

Table 1. Patient Characteristics of Those Who Had a Baseline DXA Scan before Autologous and Allogeneic Transplantation
CharacteristicsAutologous HCT (n = 102)Allogeneic HCT (n = 95)
Age at HCT (years)57 (25-74)45 (18-71)
Spine BMD at baseline (g/cm2)1.24 (0.69-1.98)1.20 (0.76-1.83)
Femur BMD at baseline (g/cm2)1.04 (0.60-1.41)1.07 (0.49-1.45)
Sex
Male64 (63%)37 (39%)
Female38 (37%)58 (61%)
Race
Non-Hispanic White89 (87%)90 (95%)
Other13 (13%)5 (5%)
Diagnosis
Acute leukemia9 (9%)59 (62%)
Lymphoma61 (60%)18 (19%)
Myeloma32 (31%)0
Other018 (19%)
Disease status at HCT
CR1/untreated42 (41%)54 (67%)
CR+2/PIF/Relapse60 (59%)41 (33%)
Time from diagnosis to HCT
Within 6 months11 (11%)43 (45%)
6 months-1 year36 (35%)26 (27%)
>1 year55 (54%)26 (27%)
Stem cell source
Bone marrow9 (9%)17 (18%)
Peripheral blood93 (91%)78 (82%)
Conditioning regimen
Myeloblative102 (100%)29 (31%)
Reduced Intensity057 (60%)
Nonmyeloblative09 (9%)
GVHD prophylaxis regimen
CsA/MTX/FKMTX/FK—27 (29%)
FK/MMF—29 (31%)
FK/MTX/MMF 38 (40%)
Donor relation
Unrelated—59 (62%)
Related—36 (38%)
HLA matched
Mismatched—21 (22%)
Matched—74 (78%)
Acute GVHD
Grade 0-1—27 (34%)
Grade II-IV—52 (66%)

BMD indicates bone mineral density; CR, complete remission; CsA, cyclosporine; DXA, dual-energy X-ray absorptiometry; GVHD, graft-versus-host disease; HLA, human leukocyte antigen; Mt, methotrexate; M, melphalan; FK, tacrolimus; MMF, mycophenolate mefetil; PIF, primary induction failure; HCT, hematopoietic cell transplantation.

For continuous variables, median (range) is presented. For categorical variables, count (percent) is presented.

Importantly, the trend of BMD loss after autologous HCT resembled that after allogeneic HCT. As summarized in Table 2, BMD loss at the spine and the femur were statistically significant in both autologous and allogeneic patients (P < .0001). The magnitude of BMD loss at the spine was similar between autologous and allogeneic HCT patients, although BMD loss at the femur was significantly higher in the allogeneic group than the autologous group. BMD loss was dramatically accelerated following HCT: the observed loss rate was 27- to 37-fold higher in the autologous group and 46- to 60-fold higher in the  allogeneic group than the expected loss rates with the normal aging process in the general population. After excluding the myeloma patients, the difference in the BMD loss rate between the autologous and allogeneic HCT groups became smaller and nonsignificant (32- and 51-fold higher at the femur and spine, respectively, in the autologous group). Within the 4-month period between the baseline and day +100 DXA scans, the BMD loss seen in autologous and allogeneic HCT patients was equivalent to aging their bones by 7 to 10 years and 13 to 17 years, respectively.

Table 2. BMD Change between Baseline and Post-HCT DXA Scans by Autologous and Allogeneic Transplantation∗
BMD MeasuresAutologous HCTAllogeneic HCT
Spine, Median (IQR)Femur, Median (IQR)Spine, Median (IQR)Femur, Median (IQR)
BMD loss, adjusted to 100 days (g/cm2)0.03 (0-0.05)0.03 (0.01-0.05)0.03 (0-0.08)0.05 (0.04-0.08)
Annualized rate of BMD loss (%)7 (0-14)9 (5-18)9 (0-19)17 (13-27)
Ratio of observed/expected annual BMD loss rate (fold)†37 (3-112)27 (12-46)60 (2-119)46 (25-73)
Years aged by the BMD loss within ∼4 months after transplant10 (1-31)7 (3-13)17 (1-33)13 (7-20)

BMD indicates bone mineral density; DXA, dual-energy X-ray absorptiometry; IQR, interquartile range; HCT, hematopoietic cell transplantation.

∗Changes in all BMD measures resulted in P < .0001 based on nonparametric tests.

†The expected annual BMD loss rate is 0.1% to 0.4% at the spine, and 0.3% to 0.6% at the femur, which varies by sex.

Over half of the patients were vitamin D deficient (25-OHD levels ≤20 ng/mL) at baseline (51%) and the prevalence nonsignificantly increased post-HCT (57%). However, there was no correlation between vitamin D levels at baseline or post-HCT, or change in vitamin D levels, with BMD changes at either the spine or the femur. Most patients had PTH levels within the normal range (12-65 pg/mL) at baseline (73%) and post-HCT (79%); the rate of hyperparathyroidism was 23% at baseline and 18% post-HCT. There was also no relationship between PTH levels and BMD change. Despite the rapid bone loss, calcium levels in most patients (94% at baseline and post-HCT) remained within the normal range (8.8-10.2 mg/dL).

We examined a number of potential predisposing risk factors present at HCT or associated with HCT therapy for BMD loss by univariate analyses. Those with a P-value ≤.10 are summarized in Table 3. There were different risk factor profiles for BMD loss in autologous and allogeneic patients. In allogeneic HCT patients, steroid dose was most strongly correlated with BMD loss at the spine (R = 0.45, P = .0004) and at the femur (R = 0.32, P = .01). Length of stay in the hospital and aGVHD were both associated with BMD change; however, after controlling for steroid dose, neither association remained. In addition, higher weight at baseline was correlated with higher BMD loss (R = 0.26, P = .05 at the spine; R = 0.24, P-value = .06 at the femur); and whereas a higher BMD at baseline was also correlated with BMD loss (R = 0.22, P = .09 at the spine; R = 0.24, P = .06 at the femur). Both weight and baseline BMD remained significant after controlling for steroid dose.

Table 3. Significant Risk Factors by Univariate Analysis for BMD Loss in Autologous and Allogeneic HCT Patients
Risk FactorAutologous HCTAllogeneic HCT
P-Value, SpineP-Value, FemurP-Value, SpineP-Value, Femur
Risk factors present at HCT
Younger age at HCT (year)N.S..004.08N.S.
Higher weight at baseline (kg)N.S.N.S..05.06
Higher BMD at baseline (g/cm2).02N.S..09.06
Diagnosis (lymphoma versus myeloma and ALL/AML).03.04N.S.N.S.
Longer time from diagnosis to HCTN.S.N.S.N.S..07
Risk factors associated with HCT
Conditioning regimen (Cy/TBI/Bu/Cy versus other).03N.S.N.S.N.S.
Longer length of stay in hospital (days)N.S.N.S..07.06
Higher steroid dose (prednisone equivalent, g)N.S.N.S..0004.01
Acute GVHD (grade 2-4 versus 0-1)——.04N.S.

BMD indicates bone mineral density; Bu, busulfan; Cy, cyclophosphamide; GVHD, graft-versus-host disease; KPS, Karnofsky performance score; N.S., nonsignificant with P > .10; HCT, hematopoietic cell transplantation; TBI, total body radiation, ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia.

P-values were derived from Pearson's correlation test for continuous covariates and Wilcoxon rank-sum test for categorical covariates. Factors with P ≤ .10 in the univariate analysis were entered and evaluated by backward elimination in the multivariate analysis (see Methods section). Factors considered in the univariate analysis, but resulted in P > .10 in all 4 BMD measures, included height, gender, disease status at HCT, KPS at HCT, GVHD prophylaxis regimen, donor relation, HLA-match, and gender match.

In autologous HCT patients, there was no association between steroid dose and BMD change. The most consistent risk factor was underlying disease: Hodgkin and non-Hodgkin lymphoma patients experienced a greater BMD loss than multiple myeloma (MM) patients (median loss in BMD: 0.036 g/cm2 versus 0.020 g/cm2, P = .03 at the spine; 0.037 g/cm2 versus 0.017 g/cm2, P = .04 at the femur, respectively). High-dose therapy regimen before autologous HCT was strongly correlated with diagnosis, and its association with change in BMD was not independent. Also, lymphoma patients received a significantly higher average daily steroid dose within the first 100 days post-HCT than MM patients (mean dose 5 mg/day versus 2 mg/day, respectively), although this exposure was much lower than the mean daily steroid dose of 19 mg/day in allogeneic HCT patients. In addition, younger age at HCT was correlated with BMD loss at the femur (R = 0.31, P = .004), but not at the spine (R = 0, P = .99). Similar to allogeneic patients, higher BMD at baseline was associated with greater BMD loss at the spine (R = 0.26, P = .02) in autologous patients; but the association was weak and nonsignificant at the femur (R = 0.13, P = .23).

Based on univariate analyses, multivariate models were constructed to assess change in BMD (see Table 4). These significant clinical risk factors explain only a small proportion of the variance in BMD change after autologous HCT (adjusted R2 = 0.12 at the spine and adjusted R2 = 0.11 at the femur). Although steroid dose is a strong risk factor for BMD change after allogeneic HCT, steroids, baseline weight, and BMD explain only 30% of variance in BMD change at the spine and 17% at the femur.

Table 4. Multivariable Models of BMD Loss by Autologous and Allogeneic HCT
BMD LossCovariatesP-ValueR2Adjusted∗ R2
Autologous HCTSpineHigher spine BMD at baseline, Hodgkin or non-Hodgkin lymphoma diagnosis.0050.150.12
FemurYounger age at HCT, Hodgkin or non-Hodgkin lymphoma diagnosis.0060.140.11
Allogeneic HCTSpineHigher weight, higher spine BMD at baseline, higher steroid dose<.00010.330.30
FemurHigher weight, higher femur BMD at baseline, higher steroid dose.0030.210.17

BMD indicates bone mineral density; HCT, hematopoietic cell transplantation.

∗R2 was adjusted based on the degrees of freedom.

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Discussion 

Our study describes a significant BMD loss in the majority of patients after autologous HCT, which is independent of steroid use and of similar severity to that seen after allogeneic HCT. Corticosteroids can be used as an antiemetic or for treatment of complications such as interstitial pneumonitis and engraftment syndrome after autologous HCT. In our study, the average steroid dose, in prednisone equivalents through day + 100 post-HCT, was 4 mg per day in autologous HCT patients, which is much lower than the average 19 mg per day in allogeneic HCT patients. The lack of association of steroid dose with BMD loss after autologous HCT may result from tolerance to low steroid doses. Although there is no established safe corticosteroid dose threshold, 2 randomized trials showed virtually no change in bone density at the spine and hip in rheumatoid arthritis patients receiving an average steroid dose of 8 mg per day 28, 29. It is also possible that corticosteroids received before transplantation as part of induction and/or salvage therapy may have extended their bone resorptive effects after autologous HCT, which would dilute the association between post-HCT steroid exposure and BMD loss. The acute post-HCT bone loss observed among autologous HCT patients may be a combined effect of pretransplant steroid exposure and other HCT-related risk factors.

Patients who had an autologous HCT for Hodgkin or non-Hodgkin lymphoma experienced significantly more BMD loss at both the spine and hip than multiple myeloma patients, which was confirmed in multivariate models. The reason for the difference in the magnitude of bone loss between myeloma and lymphoma patients may be from several factors. First, lymphoma patients received a higher average daily steroid dose in the first 100 days post-HCT than MM patients, and received different high-dose preparative regimens. Second, skeletal complications are commonly seen in MM patients 30, 31, 32, due to an increased osteoclastic bone resorption and suppressed osteoblastic bone formation from myeloma cells interacting with the bone marrow microenvironment [33]. Although bone lesions and hypercalcemia are rare in most lymphoma patients [34], there are several reports indicating that accelerated bone loss may be a common complication of lymphoma therapy 35, 36, 37, 38. Third, MM patients are frequently treated with bisphosphonates before HCT, which may have extended protection against post-HCT BMD loss. Finally, MM patients had a lower baseline BMD before transplantation compared to lymphoma patients (mean T-score −0.20 veresus +0.20, respectively), because of their underlying malignancy or treatment for it. A previous study [6], as well as our own, found a lower baseline BMD was protective of bone loss post-HCT.

The significant BMD loss seen after autologous HCT was still lower than that after allogeneic HCT, especially when comparing the ratio of observed/expected annual BMD loss rate between the 2 groups (Table 2). The higher corticosteroid dose received by allogeneic HCT patients may be one explanation for this difference and bisphosphonate treatment for myeloma patients may be another. Nearly one-third of our autologous HCTs were myeloma patients, whereas none of the allogeneic HCT patients were treated for myeloma. This subgroup of autologous HCT patients may benefit from the extended protection of bisphosphonate use pre-HCT, which may partly explain the lower rate of BMD loss seen in autologous versus allogeneic HCT patients. As noted in the results, the differences in the BMD loss rate between autologous and allogeneic HCTs became smaller and nonsignificant after excluding the MM patients from the comparison.

Although the majority (∼70%) of our allogeneic HCT patients RIC or NMA conditioning regimens, the magnitude of BMD loss was comparable to prior studies of patients who received MA regimens 6, 7, and conditioning regimen intensity was not significantly associated with bone loss after allogeneic HCT. This may be from the overwhelming effect of corticosteroid exposure or that the threshold for chemotherapy-associated bone destruction is lower than the reduced intensity dose used prior to allogeneic HCT.

In our study, vitamin D supplementation was not administered between the 2 DXA scans. Although it has been hypothesized that vitamin D deficiency-induced secondary hyperparathyroidism may be one reason for HCT-related BMD loss [39], trials of vitamin D supplementation have failed to prevent bone loss 12, 14, 19. Our data also do not support a major role of calcemic hormones including vitamin D and PTH-mediated calcium homeostasis in the accelerated bone loss after autologous or allogeneic HCT. It is possible that the levels of the active vitamin D metabolite 1,25-dihydroxyvitamin D were maintained within normal range even though the major circulating metabolite 25-OHD was low [40], resulting in undisturbed calcium homeostasis in most patients.

In summary, our prospective study found accelerated BMD loss occurred commonly after both autologous and allogeneic HCT at a similar severity, but because of different risk factors. Because antiresorptive bisphosphonate therapy has been shown to effectively prevent or reverse bone loss after allogeneic HCT, it is highly warranted to evaluate similar strategies in autologous HCT patients. More studies are needed to evaluate individual risk of BMD loss before transplantation.

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Acknowledgments 

Financial disclosure: This work was partially funded by a grant from the CALGB as a Young Investigator Award to Dr. Smiley.

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 Financial disclosure: See Acknowledgments on page 1136.

PII: S1083-8791(10)00088-1

doi:10.1016/j.bbmt.2010.02.017

Biology of Blood and Marrow Transplantation
Volume 16, Issue 8 , Pages 1130-1137, August 2010

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