Expanded question: Is hormone pellet therapy effective for maintaining bone integrity in chronic lymphocytic leukemia patients with osteoporosis?

Answered on May 1, 2024
The medical literature provides some insight into the use of hormone therapy (HT) for bone mineral density (BMD) improvement in various populations, which may offer some indirect evidence for the use of hormone pellet therapy in chronic lymphocytic leukemia (CLL) patients with osteoporosis. However, there is no direct evidence from the medical literature provided that specifically addresses hormone pellet therapy in CLL patients with osteoporosis.
In a retrospective study, continuous HT was shown to increase BMD in adolescent girls with hypogonadism after hematopoietic stem cell transplantation (HSCT).[1] Similarly, long-term subcutaneous testosterone pellet implants as replacement therapy in male hypogonadism were found to maintain normal BMD.[2] These findings suggest that hormone therapy can be beneficial for bone health in patients with hormone deficiencies due to HSCT, which is a treatment some CLL patients may undergo.
Furthermore, hormone replacement therapy (HRT) has been shown to have a positive effect on BMD in young women with premature ovarian insufficiency after allogeneic HSCT.[3] This indicates that HRT can be an important intervention for bone health in post-HSCT patients, which may be extrapolated to CLL patients with osteoporosis, although direct evidence in this specific population is lacking.
It is important to note that the management of osteoporosis in patients with hematologic conditions, including those who have undergone HSCT, should include BMD examination, evaluation of clinical risk factors, and general dietary and physical activity measures, with appropriate application of osteoporosis pharmacotherapies to patients at increased risk of bone loss and fracture.[4]
In conclusion, while hormone pellet therapy has been shown to be effective in maintaining bone integrity in other populations, such as hypogonadal men and women with premature ovarian insufficiency post-HSCT, direct evidence for its use specifically in CLL patients with osteoporosis is not provided in the medical literature. Therefore, decisions regarding the use of hormone pellet therapy in this patient population should be individualized and based on a comprehensive assessment of the patient's overall health status, risk factors, and existing evidence for hormone therapy in related conditions.

1.
Efficacy of Hormone Therapy for Osteoporosis in Adolescent Girls After Hematopoietic Stem Cell Transplantation: A Longitudinal Study.

Kodama M, Komura H, Shimizu S, et al.

Fertility and Sterility. 2011;95(2):731-5. doi:10.1016/j.fertnstert.2010.09.037.

Objective: To assess changes in bone mineral density of adolescent girls diagnosed with hypogonadism after hematopoietic stem cell transplantation (HSCT) during continuous hormone therapy (HT).

Design: Retrospective study.

Setting: Department of Obstetrics and Gynecology, Osaka Medical Center and Research Institute for Maternal and Child Health. PATIENT(S): Twenty-eight adolescent girls with hormone deficiency after HSCT. INTERVENTION(S): All patients were treated with HT. MAIN OUTCOME MEASURE(S): Bone mineral density and markers of bone metabolism were evaluated. RESULT(S): Twenty-eight patients were enrolled. The girls underwent HSCT at 10.2 ± 4.0 years of age (median ± SD).The first evaluation was performed at 15.1 ± 1.9 years of age, 3.8 ± 3.4 years after HSCT. Bone mineral density increased significantly from -2.7 ± 1.1 (Z-score) to -2.3 ± 1.2 during HT administration for 5.7 ± 2.5 years. Twenty-four of 28 patients (86%) showed a good response to HT. The levels of urinary N-telopeptides of type 1 collagen and serum osteocalcin were high at the first evaluation in 76% and 53% of patients and at the last in 76% and 18%, respectively, thereafter. CONCLUSION(S): Significant effects on bone metabolism resulting from HSCT were observed; however, HT increased bone mineral density of the hypogonadal patients.

2.
Bone Mineral Density Outcomes Following Long-Term Treatment With Subcutaneous Testosterone Pellet Implants in Male Hypogonadism.

Zacharin MR, Pua J, Kanumakala S.

Clinical Endocrinology. 2003;58(6):691-5. doi:10.1046/j.1365-2265.2003.01746.x.

Background: Osteoporosis is a common complication of untreated male hypogonadism. Even mild hypogonadism due to suboptimal testosterone replacement may result in decreased bone mineralization and osteoporosis.

Objective: To assess bone mineral density in hypogonadal men following long-term long-acting subcutaneous testosterone pellet implants as replacement therapy.

Patients: A cross-sectional study of 37 patients with primary or secondary hypogonadism receiving long-term (mean 6.6 years) subcutaneous testosterone pellet implants as replacement therapy.

Measurements: Bone mineral density was measured in all patients using dual energy X-ray absorptiometry. Serum testosterone 3-4 months after insertion of pellets was measured in all patients to assess adequacy of replacement therapy.

Results: Mean areal bone mineral density were 1.02 (SD 0.14) g/cm2 with a mean Z score of -0.64 (SD 1.3) and 0.87 (SD 0.13) g/cm2 with a mean Z score of -0.72 (SD 1.2) at lumbar spine and neck of femur, respectively. Mean serum testosterone 3-4 months after pellets insertion was 15.45 nmol/l (SD 4.2 nmol/l). There was no significant correlation between bone mineral density and patient's age at start or duration of testosterone therapy.

Conclusions: Bone mineral density in long-term regularly treated hypogonadal men was not different from the age-matched reference range for normal men. Long-acting subcutaneous testosterone pellet implants as replacement therapy in male hypogonadism are safe, acceptable to the patient, result in adequate bone mass accumulation and maintenance of normal bone mineral density. By provision of sustained physiological levels of testosterone they may contribute to increased androgen effect at the receptor level.

3.
Effects of Hormone Replacement Therapy on Bone Mass After Allogeneic Hematopoietic Stem Cell Transplantation.

Ha J, Park SS, Park S, et al.

The Journal of Clinical Endocrinology and Metabolism. 2020;105(9):dgaa406. doi:10.1210/clinem/dgaa406.

Context And Objectives: This study aimed to assess the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) in young women who underwent allogeneic hematopoietic stem cell transplantation (HSCT).

Participants And Methods: This retrospective cohort included 234 female patients with premature ovarian insufficiency (POI) who underwent allogeneic HSCT between April 2009 and April 2016 at Seoul St. Mary's Hospital in Seoul, Korea. Inclusion criteria included adult patients who were age 40 years or younger at the time of transplantation and were followed for at least 3 years after HSCT.

Results: At the first and second years after HRT, there was a significant increase in the BMD of the lumbar spine of the HRT group (n = 170) compared to that of the non-HRT group (n = 64) (P = .033 and P = .047, respectively). The BMD of the lumbar spine significantly increased from baseline by 4.16 ± 4.39% and 5.42 ± 5.86% after 1 and 2 years of HRT, respectively (P = .037 and P = .021). The BMD of the femoral neck and total hip also showed a significant percentage increase from baseline after 2 years of HRT. These changes were significant even in the presence of graft-versus-host disease or steroid exposure. For HRT that was initiated within 12 months after HSCT, the increase in BMD in the lumbar spine was greatest after 2 years of HRT.

Conclusions: These results support that early and active hormonal therapy might be beneficial for BMD in female HSCT recipients with POI.

4.
Bone Management in Hematologic Stem Cell Transplant Recipients.

Kendler DL, Body JJ, Brandi ML, et al.

Osteoporosis International : A Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2018;29(12):2597-2610. doi:10.1007/s00198-018-4669-4.

Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with some malignant and non-malignant hematological diseases. Advances in transplantation techniques and supportive care measures have substantially increased the number of long-term HSCT survivors. This has led to an increasing patient population suffering from the late effects of HSCT, of which, bone loss and its consequent fragility fractures lead to substantial morbidity. Altered bone health, with consequent fragility fractures, and chronic graft-versus-host disease (GVHD) are factors affecting long-term quality of life after HSCT. Hypogonadism, HSCT preparative regimens, nutritional factors, and glucocorticoids all contribute to accelerated bone loss and increased fracture risk. Management strategies should include bone mineral density examination, evaluation of clinical risk factors, and general dietary and physical activity measures. Evidence has accumulated permitting recommendations for more attentiveness to evaluation and monitoring of bone health, with appropriate application of osteoporosis pharmacotherapies to patients at increased risk of bone loss and fracture.