We evaluated the bone augmenting capacity of bioactive glass particles, size range 300-355 microns (BG-particles), in human sinus floor elevations using histomorphometrical methods. A total of 10 patients underwent bilateral grafting, using a 1:1 mixture of autogenous bone particles (from iliac crest) and BG-particles at one side (experimental side), and bone particles only at the other side (control side, split mouth design). A total of 72 bone biopsies were taken at the time of fixture installation; that is, 3 patients at 4 months, 3 at 5 months and 3 at 6 months after grafting and 1 patient at 16 months (when she presented again). In each case 6 biopsies were taken, 3 left and 3 right. Histomorphometry showed that in grafts at control sides, trabecular bone was present after 4 months, comprising almost 41% of the tissue volume. This bone contained viable osteocytes and was of mature lamellar type and showed a mature histological appearance. Bone volume continued to increase slightly, to 42% at 5 months, 44% at 6 months and 45% at 16 months. The graft volume at experimental sides consisted at 4 months for 28% of woven and some lamellar bone, and increased to 35% at 5 months and 38% at 6 months, when mainly lamellar bone was found. At 16 months a lamellar bone volume of 45% was found. The BG-particles transformed and became excavated with time, starting at 4 months, and their centers gradually filled with bone tissue. All BG-particles had disappeared by resorption at 16 months after grafting and had been replaced by bone tissue. Parameters of bone turnover (% osteoid surface, % resorption surface, mineral apposition rate as measured by tetracycline labeling) indicated that bone remodeling was very active at both sides, during more than 6 months, despite the mature histological appearance of the bone tissue. From these histological observations, we conclude that a 1:1 mixture of autogenous bone/BG-particles seems a promising alternative to autogenous bone only, when low amounts of bone tissue are available for sinus augmentation.

For reconstruction of the severely resorbed lateral maxilla for dental implant placement, one of the successful procedures is to elevate the maxillary sinus floor by implanting demineralized bone matrix (DBM). We studied bone formation in DBM grafts in the lateral maxilla in humans by means of histology and histomorphometry. Six months after grafting, at the time of dental implantation biopsies were taken from the grafted areas of seven patients. All biopsies contained mineralized matrix (MM) in the grafted area. At close inspection, three types of mineralization were found. First, lamellar biomineralization was seen in and near the maxillary host bone. Second, remineralization was observed in some particles that probably had not been completely demineralized. In the area connecting the graft and host bone, where woven bone was formed against DBM particles, a third mechanism was detected. In this case many dotlike foci of remineralization appeared close to the bone-DBM interface. The remineralized DBM and woven bone were both subsequently remodeled. Bone formation was most active in the area adjoining the maxillary host bone. We conclude that in human sinus floor elevation, allogenic DBM increases mineralized tissue volume by osteoconduction that is supported by the remineralization processes. Osteoinduction by this material seems questionable.

Bone morphogenetic proteins have proven to be effective bone inductors in animals and are therefore promising as inductors of bone formation in humans. In the present study we investigated the tissue formed after grafting osteogenic protein 1 on a collagen carrier (OP-1-device) in the human sinus floor elevation procedure. Three patients were grafted with OP-1 device. For comparison 3 groups of 3 patients were included in the study receiving respectively, autogenous bone, human freeze-dried demineralized bone matrix (DBM) or no graft. This last group had a sufficient alveolar bone height for dental implantation. Six months after grafting, at the time of implantation, biopsies were taken from the grafted area and/or the future dental positions. Undecalcified sections were used for histological and histomorphometrical analysis. All grafted sinuses showed an increased osteoid percentage when compared to non-grafted sinuses. Autogenous bone grafts all showed lamellar bone formation. In the DBM grafts mostly woven bone had been formed, predominantly by what appeared to be osteo-conduction. The OP-1 device gave rise to bone formation in 2 of the 3 patients. After 6 months implants could only be placed in 1 out of the 3 patients treated with OP-1 device. This patient showed mature lamellar bone formation, comparable to autogenous bone grafts. In the second patient all bone found was woven and the presence of a high osteoid percentage and large osteocyte lacunae indicated that this was recently-formed bone. Remnants of the collagen carrier were rare and new bone was never found against them, suggesting that this bone was formed by osteo-induction. In the third patient no new bone had been formed. The device had been encapsulated with fibrous tissue and inflammatory reaction was present. We conclude that in the human sinus floor elevation OP-1 has potential bone inductive capacity, but that results in the 3 patients tested with the current OP-1 device are inconsistent.

Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P < 0.05). Trabecular bone turnover and structural parameters in the proximal femur were not affected by exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone structure with increased marrow cavity and a decreased number of trabeculae. In conclusion, mechanical loading has beneficial effects on BMC and BMD of the ovariectomized rat. This indicates that the load in the backpack was high enough to elicit an osteogenic response sufficient to compensate for the ovariectomy-induced bone loss. The results confirm that estrogen suppresses both bone resorption and bone formation in the proximal metaphysis in the femoral head of our rat-with-backpack model. The effects of mechanical loading on the trabecular bone of the femoral head were not significant. This study suggests that the effect of mechanical loading in the rat-with-backpack model mainly occurs at cortical bone sites.

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Type 2 (non-insulin-dependent) diabetes mellitus is associated with increased glucose, insulin, total and VLDL-triglyceride, and often total and LDL-cholesterol levels which promote vascular disease. Recombinant human insulin-like growth factor-I which mimics many effects of insulin, decreased insulin, total and VLDL-triglyceride, and total and LDL-cholesterol levels in healthy man as well as glucose and insulin levels in Type 2 diabetic patients. We, therefore, investigated total and fractionated triglyceride and cholesterol levels, lipoprotein(a), non-esterified fatty acid, and apolipoprotein levels in eight Type 2 diabetic patients during five control, five treatment, and three wash-out days. They received a constant diet throughout and daily 2 x 120 micrograms insulin-like growth factor-I/kg s.c. during the treatment period. Fasting total and VLDL-triglyceride, total and LDL-cholesterol control levels were (mean +/- SD) 3.1 +/- 2.6, 1.3 +/- 1.0, 6.3 +/- 1.3, and 4.5 +/- 1.1 mmol/l and decreased to 1.6 +/- 0.8, 0.6 +/- 0.4, 5.0 +/- 1.0, and 3.5 +/- 1.1 mmol/l, respectively, on the last treatment day (p < 0.01). During therapy, fasting lipoprotein(a) levels and the postprandial area under the triglyceride curve decreased by 48 +/- 22 and 32 +/- 18% of control (p < 0.01), respectively. In conclusion, insulin-like growth factor-I lowered lipid levels in Type 2 diabetic patients directly or indirectly or both because of decreased glucose and insulin levels. Long-term trials would be of interest with respect to the cardiovascular risk in Type 2 diabetes and patients with hyperlipidaemia.

The effect of pamidronate therapy on bone histology was studied in patients with osteoporosis with at least one vertebral fracture in a randomized, double-masked, placebo-controlled, multi-center trial. Patients received pamidronate 150 mg/day or placebo in addition to calcium 500 mg/day and vitamin D3 400 IU/day. Transiliac bone biopsies were obtained before and after 1 or 2 years of treatment. Of these, 23 pairs of biopsies obtained from 14 women and 9 men (mean age +/- SD, 61.5 +/- 10 years) were of sufficient quality for histomorphometry. Histomorphometry was performed on sections stained with Goldner's trichrome, using a drawing tube and a digitizer. Urinary hydroxyproline excretion decreased significantly (p < 0.005) following pamidronate treatment, indicating a decrease in bone resorption. Osteoid volume and osteoid surface also decreased significantly in the pamidronate group (p < 0.004 and p < 0.003 respectively), consistent with a secondary decrease in bone formation. Osteoid variables did not change in the placebo-treated patients. Cortical thickness, trabecular bone volume and trabecular thickness did not change after pamidronate or placebo treatment. Wall thickness, however, showed a borderline increase following pamidronate treatment. After pamidronate, eroded surface and mineral apposition rate did not change significantly in the placebo and pamidronate groups. Mineralizing surface and activation frequency showed a borderline decrease in the placebo and pamidronate groups. The decrease in mineralization lag time was of borderline significance in the pamidronate group, corroborating the absence of any negative effect on mineralization. In conclusion, pamidronate treatment led to a decrease in bone turnover and did not interfere with bone mineralization.

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