Naim Maalouf - Academia.edu (original) (raw)
Papers by Naim Maalouf
Kidney …, 2008
A 52-year-old white female with a history of profound hypophosphatemia, muscle weakness, and mult... more A 52-year-old white female with a history of profound hypophosphatemia, muscle weakness, and multiple debilitating atraumatic fractures was referred in March 2004 for evaluation at the Mineral Metabolism Clinic. Five years prior, she had sustained bilateral rib fractures which failed to heal. In May 2000, she was diagnosed with primary hyperparathyroidism based on serum calcium of 10.4 mg/dl (reference range 8.4-10.2 mg/dl), parathyroid hormone (PTH) of 97 pg/ml (reference 10-65 pg/ml), phosphorus of 2.0 mg/dl (reference 2.5-4.5 mg/dl), and alkaline phosphatase of 420 IU/l (reference 38-126 IU/l). Bone density measured by dual energy X-ray absorptiometry (DXA) revealed T-scores of −2.9 (lumbar spine) and −3.5 (femoral neck), indicative of osteoporosis. In July 2000, the patient underwent partial parathyroidectomy with removal of two parathyroid glands (histologic diagnosis: adenoma for left superior gland, normal for left inferior gland). Intraoperatively, serum PTH fell from 58 to 13 pg/ml at 24 min post-excision. In the ensuing months, serum calcium normalized, but PTH remained elevated and serum phosphorus remained low. One year after the first parathyroid surgery, the patient underwent a subtotal parathyroidectomy (histologic diagnosis: hyperplasia), leaving only about 20-30 mg of the right inferior gland, and was placed on low dose calcitriol (0.5 μg daily). Over the next three years, she progressively lost mobility due to muscle weakness, requiring assistance in ambulation. She developed multiple additional atraumatic fractures (bilateral superior and inferior pubic ramus, bilateral femoral head, radial neck, ulnar, and multiple vertebral) resulting in kyphosis. After repeated neurological and rheumatological evaluations, she was referred to our clinic. In June 2004, she complained of profound fatigue and severe pain in the low back and thoracic area and required a walker for ambulation. Physical examination revealed a well-nourished kyphotic woman, with a widebased gait and generalized decreased muscle strength (4/5). An iliac crest bone biopsy and clinical biochemistry evaluation were performed. BONE BIOPSY The bone biopsy (Figure 1) revealed a marked increase in osteoid parameters for both cortical and cancellous bone, including osteoid volume (11.9 and 56.1% of total bone volume, for cortical and cancellous bone respectively), osteoid surface (78.9 and 93.6% of total bone
The Journal of Clinical Endocrinology & Metabolism, 2005
Alendronate, an inhibitor of bone resorption, is widely used in osteoporosis treatment. However, ... more Alendronate, an inhibitor of bone resorption, is widely used in osteoporosis treatment. However, concerns have been raised about potential oversuppression of bone turnover during long-term use. We report on nine patients who sustained spontaneous nonspinal fractures while on alendronate therapy, six of whom displayed either delayed or absent fracture healing for 3 months to 2 yr during therapy. Histomorphometric analysis of the cancellous bone showed markedly suppressed bone formation, with reduced or absent osteoblastic surface in most patients. Osteoclastic surface was low or low-normal in eight patients, and eroded surface was decreased in four. Matrix synthesis was markedly diminished, with absence of double-tetracycline label and absent or reduced single-tetracycline label in all patients. The same trend was seen in the intracortical and endocortical surfaces. Our findings raise the possibility that severe suppression of bone turnover may develop during long-term alendronate therapy, resulting in increased susceptibility to, and delayed healing of, nonspinal fractures. Although coadministration of estrogen or glucocorticoids appears to be a predisposing factor, this apparent complication can also occur with monotherapy. Our observations emphasize the need for increased awareness and monitoring for the potential development of excessive suppression of bone turnover during long-term alendronate therapy.
Kidney …, 2008
A 52-year-old white female with a history of profound hypophosphatemia, muscle weakness, and mult... more A 52-year-old white female with a history of profound hypophosphatemia, muscle weakness, and multiple debilitating atraumatic fractures was referred in March 2004 for evaluation at the Mineral Metabolism Clinic. Five years prior, she had sustained bilateral rib fractures which failed to heal. In May 2000, she was diagnosed with primary hyperparathyroidism based on serum calcium of 10.4 mg/dl (reference range 8.4-10.2 mg/dl), parathyroid hormone (PTH) of 97 pg/ml (reference 10-65 pg/ml), phosphorus of 2.0 mg/dl (reference 2.5-4.5 mg/dl), and alkaline phosphatase of 420 IU/l (reference 38-126 IU/l). Bone density measured by dual energy X-ray absorptiometry (DXA) revealed T-scores of −2.9 (lumbar spine) and −3.5 (femoral neck), indicative of osteoporosis. In July 2000, the patient underwent partial parathyroidectomy with removal of two parathyroid glands (histologic diagnosis: adenoma for left superior gland, normal for left inferior gland). Intraoperatively, serum PTH fell from 58 to 13 pg/ml at 24 min post-excision. In the ensuing months, serum calcium normalized, but PTH remained elevated and serum phosphorus remained low. One year after the first parathyroid surgery, the patient underwent a subtotal parathyroidectomy (histologic diagnosis: hyperplasia), leaving only about 20-30 mg of the right inferior gland, and was placed on low dose calcitriol (0.5 μg daily). Over the next three years, she progressively lost mobility due to muscle weakness, requiring assistance in ambulation. She developed multiple additional atraumatic fractures (bilateral superior and inferior pubic ramus, bilateral femoral head, radial neck, ulnar, and multiple vertebral) resulting in kyphosis. After repeated neurological and rheumatological evaluations, she was referred to our clinic. In June 2004, she complained of profound fatigue and severe pain in the low back and thoracic area and required a walker for ambulation. Physical examination revealed a well-nourished kyphotic woman, with a widebased gait and generalized decreased muscle strength (4/5). An iliac crest bone biopsy and clinical biochemistry evaluation were performed. BONE BIOPSY The bone biopsy (Figure 1) revealed a marked increase in osteoid parameters for both cortical and cancellous bone, including osteoid volume (11.9 and 56.1% of total bone volume, for cortical and cancellous bone respectively), osteoid surface (78.9 and 93.6% of total bone
The Journal of Clinical Endocrinology & Metabolism, 2005
Alendronate, an inhibitor of bone resorption, is widely used in osteoporosis treatment. However, ... more Alendronate, an inhibitor of bone resorption, is widely used in osteoporosis treatment. However, concerns have been raised about potential oversuppression of bone turnover during long-term use. We report on nine patients who sustained spontaneous nonspinal fractures while on alendronate therapy, six of whom displayed either delayed or absent fracture healing for 3 months to 2 yr during therapy. Histomorphometric analysis of the cancellous bone showed markedly suppressed bone formation, with reduced or absent osteoblastic surface in most patients. Osteoclastic surface was low or low-normal in eight patients, and eroded surface was decreased in four. Matrix synthesis was markedly diminished, with absence of double-tetracycline label and absent or reduced single-tetracycline label in all patients. The same trend was seen in the intracortical and endocortical surfaces. Our findings raise the possibility that severe suppression of bone turnover may develop during long-term alendronate therapy, resulting in increased susceptibility to, and delayed healing of, nonspinal fractures. Although coadministration of estrogen or glucocorticoids appears to be a predisposing factor, this apparent complication can also occur with monotherapy. Our observations emphasize the need for increased awareness and monitoring for the potential development of excessive suppression of bone turnover during long-term alendronate therapy.