The Scope Of The Problem In Prostate Cancer

We became aware of the problems of bone mineral density loss when, within the space of 1 year, three of the author's patients suffered hip fractures. We then began to evaluate our patients who were being treated with androgen deprivation therapy (ADT) with DEXA scans. Of our 75 patients studied to date, 70 were on leuprolide therapy and five had undergone bilateral orchiectomy.10 All patients underwent an in-office screening DEXA scan utilizing the fourth digit of the nondominant hand. When this proved abnormal, a full table body scan of the hip and spine was performed for comparison. The patients' ages ranged from 46 to 98, with a mean of 76.4. The patients' duration of ADT ranged from just beginning treatment to 13 years on therapy, with an average of 3.35 years. Of the entire series, only 34 (45.4%) had a normal bone mineral density. Of the 41 patients with abnormal DEXA scans, 25 (61%) had osteopenia, while 16 (39%, or 21.3% of the entire group of

75 men) had osteoporosis.

When we examined the men by age, we found that the men over the age of 70 had a greater risk of loss of bone mineral density than men less than 70. Overall, 68.4% of the men less than 70 years of age had a normal bone mineral density, compared to only 37.5% of the men over 70. Of the 25 men with osteopenia, 19 (76%) were older than 70, while all of the 16 men with osteoporosis were over 70. Duration of therapy also appeared to be important. We examined the 34 men who were on treatment for less than 2 years and compared their DEXA results to the men on ADT for more than 2 years. Of the less than 2 year group, 58.8% had a normal DEXA scan, while only 34% of the men on treatment for more than 2 years had a normal DEXA scan. We further examined the 34 men on therapy for less than 2 years, and found that those with normal bone mineral density had an average age of 72.4 years, while those with abnormal DEXA scans, had an average age of 81.3. We examined the men by the number of years on therapy and as the duration of therapy became longer, the bone mineral density decreased. Thus, from our own work, we conclude that the older the man is and the longer he is on ADT, the likelier he is to experience a loss in bone mineral density. Other interesting studies have confirmed our results.

Smith and associates initially reported on 41 men with locally advanced prostate cancer, without metastatic disease, and who had not yet undergone ADT.11 These men then underwent DEXA scan of the hip and spine. The mean age in this series was 68. Of this group of men, 66% had normal bone densities, while 29% had osteopenia and 5% had osteoporosis. This compares very favorably to our findings in men on therapy for less than 2 years.

Stoch etal. studied three groups of men: group 1 consisted of controls solicited via a newpaper advertisement; group 2 were men with cancer of the prostate, but not on ADT; and group 3 were men on ADT for at least 6 months, with a mean of 41 months of therapy.12 The men underwent evaluation of bone mineral density by a variety of techniques including finger, spine and hip DEXA scans. They found that the normal rate of bone loss due to aging is 0.5-1.0% per year, but that LHRH analog therapy was associated with more than a decade increase in this loss. They also reported an incidence of osteoporotic fractures similar to other groups.

Kiratli etal. studied 36 patients from baseline to 10 years after initiation of ADT therapy for bone mineral density with DEXA scans.13 They also found an increasing trend for loss of bone mineral density over time, more pronounced in the hip. Surgical castration appeared to be more likely than LHRH analogs to lead to a loss in bone density. They evaluated intermittent LHRH analog therapy and concluded that after 6 years there was a trend toward less bone mineral density loss with this therapy; however, their numbers were quite small.

Daniell performed two studies on osteoporosis and ADT. In the first paper, he reviewed the records of 235 men with prostate cancer, and from this culled the names of 17 men who had undergone orchiectomy between 1983 and 1990, and were still alive in 1995.14 He then performed DEXA scans of the femoral neck and compared the results to 23 controls. He found ten osteoporotic fractures in the larger group, eight of which were found in the 17 orchiectomy patients. Of the 16 men who survived for >60 months, six had osteoporotic fractures and reduced bone mineral density on DEXA scans. The incidence continued to increase over time (Fig. 44.1). In a follow-up study, Daniell evaluated 26 men prior to orchiectomy or LHRH

Years

Fig. 44.1. Osteoporotic fracture incidence.

Years

Fig. 44.1. Osteoporotic fracture incidence.

analog therapy and followed them for 6-42 months, comparing them to 12 controls.15 They found that bone mineral density in the ADT patients fell about 4% per year for years 1-2, and 2% per year every year thereafter. The loss continued at a pace of 1.4-2.6% per year for years 3-8. Both orchiectomy and LHRH analog therapy were likely to cause this loss.

Hatano et al. studied 218 men treated for 6 months or more with LHRH analogs for prostate cancer.16 Fourteen of these patients (6%) developed a bone fracture during their treatment. The bone density of the lumbar vertebrae was measured by quantitative computed tomography (QCT) scan. The average age was of the men was 78 years and the duration of therapy ranged from 11 to 46 months (average 28 months). The bone density was significantly lower in the patients with a fracture than in those without. Of the patients with a fracture, 12 out of 14 had a good recovery but two patients (one lumbar and one hip fracture) cannot walk unaided. In the patients with a fracture, the duration of therapy was longer (28 vs. 18 months, P < 0.05).

Preston et al. evaluated 38 patients with prostate cancer who were treated with LHRH analog or orchiectomy with or without antiandrogen therapy and 38 aged-matched controls not on androgen deprivation therapy were compared.17 Bone mineral density was measured using DEXA scans of the forearm, femoral neck, trochanter, total hip and spine, every 6 months up to 24 months. The mean age of the treated patients was 73.7 years and the duration of therapy was 29.6 months. The bone mineral density changed significantly between the groups over time at all sites except the lumbar spine, with the treated patients having a greater loss of bone mineral density.

Wei and associates studied 32 men with prostate cancer who were about to begin androgen deprivation therapy or who had been on therapy for more than 1 year.18 Bone mineral density was measured by DEXA scan of the spine, hip and forearm. Of the eight men not yet on androgen deprivation therapy, 63% had osteopenia or osteoporosis. Of the 24 men on treatment for more than 1 year, 88% were abnormal.

Eriksson et al. compared two groups of men on hormone therapy for prostate cancer: group 1 (11 patients) were treated with orchiectomy alone, while group 2 (16 patients) underwent orchiectomy plus estrogen therapy (IM or PO).1 They then measured bone mineral density of the femoral neck, trochanter and Ward's Triangle. There was a decrease in bone mineral density in the orchiectomy-only patients, which was not seen in the orchiectomy plus estrogen patients. Statistical significance was achieved only in the forearm.

Townsend and associates reviewed the records of 224 prostate cancer patients treated with LHRH analogs in order to determine the incidence of fractures. The duration of treatment was from 1 to 96 months.19 In all 22 fractures (9%) were found, with 5% of the fractures attributed to osteoporosis. However, DEXA scans were not performed and a great number of the 36% attributed to trauma may have also had underlying bone density weakness, with fractures precipitated by otherwise a minor trauma.

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